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New Life for an Old Antibiotic
Abstract
Restoring the antibacterial properties of existing antibiotics is of great concern. Herein, we present, for the first time, the formation and deposition of stable antibiotic nanoparticles (NPs) on graphene oxide (GO) sheets by a facile one-step sonochemical technique. Sonochemically synthesized graphene oxide/tetracycline (GO/TET) composite shows enhanced activity against both sensitive and resistant Streptococcus aureus (S. aureus). The size and deposition of TET NPs on GO can be controlled by varying the sonication time. The synthesized NPs ranged from 21 to 180 nm. Moreover, ultrasonic irradiation does not cause any structural and chemical changes to the TET molecule as confirmed by Fourier transform infrared spectroscopy (FTIR). The virtue of π - π stacking between GO and TET facilitate additionally the coating of TET NPs upon GO. A time dependent release kinetics of TET NPs from GO`s surface is also monitored providing important insights regarding the mechanism of antibacterial activity of GO/TET composites. Our results show that the GO/TET composite is bactericidal in nature, resulting in similar values of minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). This composite is found to be active against TET resistant S. aureus at a concentration four times lower than the pristine TET. The sensitive S. aureus follows the same trend showing six times lower MIC values compared to pristine TET. GO shows no activity against both sensitive and resistant S. aureus even at a concentration as high as 1 mg/mL, but influences the biocidal activity of GO/TET composite. We propose that the unique structure and composition manifested by GO/TET composites may be further utilized for different formulations of antibiotics with GO. The sonochemical method used in this work can be precisely tailored for the stable deposition of a variety of antibiotics on the GO surface to reduce health risks and increase the spectrum of applications.
... Despite some promising results, most of the above discussed antibacterial agents may induce cytotoxicity and inflammatory responses limiting their clinical applications. Nanoantibiotics (NPs of antibiotics) are new antibacterial agents able to solve these drawbacks and improved the efficiency of antibiotics against drug resistant bacteria [216]. For example, penicillin, discovered in 1928, is still in used despite of its limited bactericidal effect towards antibiotic resistant bacterial strains. ...
... Tetracycline (TET) is a broadspectrum antibiotic that increased its bactericidal effect against both TET sensitive and TET resistant bacterial strains after sonochemically induced transformation into nanoparticles (TETNPs) [219].TETNPs have been also deposited on graphene oxide sheets by a facile one-step sonochemical technique. Sonochemically synthesized graphene oxide/TET composite showed an enhanced activity against both sensitive and resistant S. aureus compared to the same concentration of non-transformed TET [216]. Sonochemistry was also used to simultaneously generate and deposit TETNPs onto parylene-C coated glass slides with potential to counteract pathogenic bacterial growth. ...
Bacteria that colonize and form biofilms on living tissues and medical devices are a global healthcare concern. They cause life threatening infections and are associated with increased mortality and morbidity in the hospitals. Although antibiotics have been successfully applied for treatment of bacterial diseases, the adaptive and genetic changes of the microorganisms within the biofilms make them inherently resistant to all known antibacterial agents. Therefore, novel antimicrobial strategies that do not exert selective pressure on bacterial population and minimize the risk of resistance occurrence have been sought to prevent and treat biofilm related infections. A critical overview of the numerous groups and the rationale of advanced materials and surfaces with antibacterial and antibiofilm properties is the aim of this review. The development of antibiofilm coatings based on molecules interfering with bacterial cell-to-cell communication and biofilm integrity are discussed. Nano-scale transformation of obsolete antibiotics and surface functionalization with bacteriophages and natural antibacterials including enzymes, antimicrobial peptides, and polyphenols are also considered. Finally, recent efforts to design new generation of integrated antibacterial materials are reported.
... ბვ ასოცირებულია ორსულობის, მშობიარობის, ლოგინობის ხანის, აგრეთვე მრავალ სხვადასხვა გინეკოლოგიურ გართულებასთან [1,3,11]. ბვ-ის მკურნალობა მოიცავს 2 კომპონენტს: I -ანტიმიკრობული (ანტიბიოტიკი; ანტისეპტიკი), II -პრობიოტიკი (ლაქტობაქტერიები) [4,5]. ...
Comparative analysis of 3 therapeutical schemes was made. 42 patients of the I group used antibiotic and then probiotic; 40 patients of II group received antiseptic and then probiotic. 38 patients of III group were using antiseptic and then estriol containing probiotic. Both combinative schemes, applied in the I and II groups, were characterized by the identical results. Maximal effectiveness of therapy was achieved in the III group.
... The synergistic effects of CNMs and antibiotics produces a composite with an increased antibacterial activity compared to its individual counterparts [161e163]. Association of GO and Tetracycline (TET) was reported to enhance the interaction between the antibiotic substance and microorganisms [164]. Two modes of contact influenced by GO were observed such as the wrapping of the nanocomposite on the resistant bacteria. ...
Carbon Nanomaterials present many exceptional properties, including antimicrobial ones. The transfer of the latter through their incorporation into materials has generated a growing interest with a significant increase in number of publications since 2011. The use of polymeric matrices presents many advantages, because polymers are efficient nanoparticles holders and also exhibit intrinsic antimicrobial properties in some cases. The state of the art of fabrication methods and presumed antimicrobial mechanism is presented, focusing on antibacterial activity as the latter is, by far, the most discussed in the literature. Even if many examples of such nanocomposites are available, most of them correspond to carbon nanomaterials incorporated in the volume, while only the surface is of interest in terms of intrinsic (and thus expected long-term) activity, and there is still a lack of information concerning the occurring antimicrobial mechanisms. We have identified the good stability of carbon nanomaterials in biological environment as an interesting option in terms of durability of the antimicrobial effect and will discuss this question in detail, as well as the fact that there are currently no clear conclusions concerning toxicity aspects due to the possible release of such nanoparticles in use conditions.
... The resistant bacterial species list includes multidrug resistant (MDR) and extremely drug-resistant (XDR) bacteria. These bacterial strains have evolved to exhibit resistance to almost all commercially available antibiotics, affecting millions worldwide [139]. Because of this, there are reports of the addition to ABCs with antimicrobial agents, such as quaternary amine dimethacrylate iodine comonomer [140], quaternary amine dimethacrylate comonomer [141], gold nanoparticles [142], 2-methacryloyloxyethyl phosphorylcholine, quaternary ammonium dimethylaminohexadecyl methacrylate [143], and Ag 2 O [144], different from the antibiotics. ...
Acrylic bone cements (ABC) are widely used in orthopedics for joint fixation, antibiotic release, and bone defect filling, among others. However, most commercially available ABCs exhibit a lack of bioactivity and are susceptible to infection after implantation. These disadvantages generate long-term loosening of the prosthesis, high morbidity, and prolonged and expensive treatments. Due to the great importance of acrylic bone cements in orthopedics, the scientific community has advanced several efforts to develop bioactive ABCs with antibacterial activity through several strategies, including the use of biodegradable materials such as chitosan (CS) and nanostructures such as graphene oxide (GO), with promising results. This paper reviews several studies reporting advantages in bioactivity and antibacterial properties after incorporating CS and GO in bone cements. Detailed information on the possible mechanisms by which these fillers confer bioactive and antibacterial properties to cements, resulting in formulations with great potential for use in orthopedics, are also a focus in the manuscript. To the best of our knowledge, this is the first systematic review that presents the improvement in biological properties with CS and GO addition in cements that we believe will contribute to the biomedical field.
... The combination of GFNs and traditional antibiotic is a promising solution. After combined with GO, tetracycline is found to enhance bactericidal activity against resistant S. aureus and the efficacy of GO/ tetracycline is four to six times higher than that of pristine tetracycline [148]. The amplifying effect applies to ciprofloxacin as well. ...
Antibacterial coating is widely used in health care, food service, and hospital for disinfection and microbial control. As the most popular nanomaterial nowadays, graphene family nanomaterials (GFNs), especially materials coupled with GFNs, exhibit remarkable antibacterial properties. GFNs are used in three forms, namely, the single-component form; mixed with other antibacterial agents, such as silver and photocatalysts; and combined with a base material, such as polymer and MOFs. This paper provides a general overview of the GFN-containing antimicrobial nanomaterials that are available to design antibacterial coatings or films. First, the antimicrobial performances of single-GFNs are introduced briefly. Second, the main antibacterial mechanisms of single-GFNs are presented in detail. In the following sections, GFN-based composites that are functionalized using other materials, including Ag, metal nanoparticles (or metal oxide), photocatalysts, polymers, antibiotic, enzyme, and multicomponent, to enhance their antibacterial ability are reviewed thoroughly. Then, the antibacterial mechanisms of GFNs-based composite are briefly summarized. In addition, practical applications of GFN-based coatings and films for disinfection and health protection are also put forward and discussed in detail. This review would provide valuable information to new material synthesis and practical application of GFNs-based composite.
... The MIC is recognized as the lowest concentration that inhibits any visible growth of bacteria after 24 h of incubation at 37°C [51]. The MIC values against E. coli and S. aureus of GO, pGO and pGO-TCH nanostructures are listed in table 1 and the MIC pictures are shown in the Supporting Information ( figure S2). ...
With the high demand for developing novel composites with integrated performance, graphene-based nanostructures have been drawing great attention in environmental and biomedical applications because of their extraordinary physicochemical properties and biocompatibility. Although graphene oxide (GO) nanosheets exhibit some antibacterial activities, novel GO based nanostructures with enhanced antibacterial activities are highly desired. To realize this aim, polyethyleneimine (PEI) modified GO as a tetracycline hydrochloride (TCH) carrier and release platform was constructed (pGO-TCH). The nanostructures were fully characterized by TEM, AFM, FTIR and Raman spectra, which demonstrated that TCH were uniformly and compactly deposited on PEI modified GO nanosheets. The antibacterial performances of the prepared nanostructures were investigated by disk diffusion method and bacterial growth kinetics method towards Gram-positive S. aureus and Gram-negative E. coli. Results show that pGO-TCH nanostructures exhibit good antibacterial behavior. The mechanism of antibacterial activity was studied. Moreover, the nanostructures showed good cytocompatibility. This study not only highlights a promising pGO-TCH nanostructure as a candidate of graphene-based antibacterial agent, but also provides us antibacterial mechanism between bacteria and graphene-based nanomaterials.
... There have been many structural alteration studies on antibiotics to struggle against this phenomenon [48]. Because of the potential antibacterial applications of graphene and graphene-based nanocomposites [49], conjugation of existing antibiotics with graphene-based materials is a promising solution to prevent antibacterial resistance [50,51]. ...
One of the ways of fully securing the presence of fresh water is water treatment process. Nanomaterials and nanotechnology offers an innovative solution for water treatment. In this study, physical, chemical and microbiological improvement rates of raw water were analyzed after filtration with graphene oxide. Graphene oxide's water treatment performance; silver nanoparticles, silver nanoparticles & graphene oxide composites that are commonly used in water treatment were compared with a traditional treatment method. When compared to the traditional method, there were improvements of 50 %, 40.7 %, 86.8 % and 45.5 % for color, TIC, TOC and hardness properties, respectively in water treatment by GO-based filtration with solid liquid ratio of 0.7 % (v/v). In water treatment with GO-Ag based filtration, 39.8 %, 69.8 %, 10.3 % and 28.6 % of improvements were obtained for TIC, TOC, hardness and LSI value compared to the conventional method. Both GO at 0.7 % (v/v) solid-liquid ratio and GO-Ag nanocomposites were successful in the number of total viable microorganisms and inhibiting microorganisms such as Escherichia coli fecal (gaita-infected), Salmonella typhi, Enterococcus faecalis, Pseudomona aeruginosa and Staphylococcus aureus. Among the studied parameters GO-Ag nanocomposites found to be the most suitable for drinking water treatment.
... There have been many structural alteration studies on antibiotics to struggle against this phenomenon [48]. Because of the potential antibacterial applications of graphene and graphene-based nanocomposites [49], conjugation of existing antibiotics with graphene-based materials is a promising solution to prevent antibacterial resistance [50,51]. ...
One of the ways of fully securing the presence of fresh water is water treatment process. Nanomaterials and nanotechnology offers an innovative solution for water treatment. In this study, physical, chemical and microbiological improvement rates of raw water were analyzed after filtration with graphene oxide. Graphene oxide's water treatment performance; silver nanoparticles, silver nanoparticles & graphene oxide composites that are commonly used in water treatment were compared with a traditional treatment method. When compared to the traditional method, there were improvements of 50 %, 40.7 %, 86.8 % and 45.5 % for color, TIC, TOC and hardness properties, respectively in water treatment by GO-based filtration with solid liquid ratio of 0.7 % (v/v). In water treatment with GO-Ag based filtration, 39.8 %, 69.8 %, 10.3 % and 28.6 % of improvements were obtained for TIC, TOC, hardness and LSI value compared to the conventional method. Both GO at 0.7 % (v/v) solid-liquid ratio and GO-Ag nanocomposites were successful in the number of total viable microorganisms and inhibiting microorganisms such as Escherichia coli fecal (gaita-infected), Salmonella typhi, Enterococcus faecalis, Pseudomona aeruginosa and Staphylococcus aureus. Among the studied parameters GO-Ag nanocomposites found to be the most suitable for drinking water treatment.
... В соответствии с этими положениями проводится поиск способов сохранения эффективности имеющихся антибиотиков, в том числе путем создания условий повышения чувствительности патогенов к антимикробным веществам [2]. ...
Objective. To evaluate the efficiency of combined use of antibiotics and probiotics in patients with bacterial vaginosis and trichomoniasis. Material and methods. Based on subjective and objective (pH and redox potential, the number of lactobacilli, T. vaginalis, A. vaginae, G. vaginalis, Amsel, Nugent and Hay-Ison scoring criteria) parameters, the investigators evaluated the efficiency of combined use of oral metronidazole and the intravaginal probiotic lactoginal. The control group received traditional therapy. Results. The use of probiotics in combination with metronidazole led to a more intense normalization of the physicochemical and microbiological parameters of the biotope. The efficiency of this therapy regimen was 80%, while that of traditional therapy was 20%. Conclusion. Potentiation of the antimicrobial activity of antibiotics by probiotics has been confirmed in vivo. Probiotics that potentiate the activity of antibiotics are able to replenish the function of the normal microflora during antibiotic therapy. A question is raised as to the need for a new indication for the use of probiotics – to improve the efficiency of antibiotic therapy.
... However, first generation quinolones are no longer used in therapy because of their unfavorable physicochemical profiles, lower tissue penetration and narrower antibacterial spectrum in comparison to the following generations of quinolones 7 . Nanotechnology could offer a tremendous opportunity to recycle these "old" drugs and give them a new life by delivering them in an optimized manner [8][9][10] . ...
Nowadays, biodegradable polymers such as poly(lactic acid) (PLA), poly(D,L-lactic-co-glycolic acid) (PLGA) and poly(ε-caprolactone) (PCL) remain the most common biomaterials to produce drug-loaded nanoparticles (NPs). Pipemidic acid (PIP) is a poorly soluble antibiotic with a strong tendency to crystallize. PIP incorporation in PLA/PLGA NPs was challenging because of PIP crystals formation and burst release. As PIP had a poor affinity for the NPs, an alternative approach to encapsulation was used, consisting in coupling PIP to PCL. Thus, a PCL–PIP conjugate was successfully synthesized by an original drug-initiated polymerization in a single step without the need of catalyst. PCL–PIP was characterized by NMR, IR, SEC and mass spectrometry. PCL–PIP was used to prepare self-assembled NPs with PIP contents as high as 27% (w/w). The NPs were characterized by microscopy, DLS, NTA and TRPS. This study paves the way towards the production of NPs with high antibiotic payloads by drug-initiated polymerization. Further studies will deal with the synthesis of novel polymer–PIP conjugates with ester bonds between the drug and PCL. PIP can be considered as a model drug and the strategy developed here could be extended to other challenging antibiotics or anticancer drugs and employed to efficiently incorporate them in NPs.
... The nano-sized transformation of another antibiotic TET also improved its bactericidal activity, killing both TET sensitive and resistant bacteria (Shimanovich et al. 2015). Sonochemically synthesised graphene oxide/TET nanocomposites demonstrated enhanced activity against both sensitive and resistant S. aureus when compared to the same concentration of nontransformed antibiotic (Mishra et al. 2015). TET loaded in protein microspheres showed high bactericidal effect against E. coli and S. aureus (Avivi et al. 2003). ...
Drug resistance occurrence is a global healthcare concern responsible for the increased morbidity and mortality in hospitals, time of hospitalisation and huge financial loss. The failure of the most antibiotics to kill “superbugs” poses the urgent need to develop innovative strategies aimed at not only controlling bacterial infection but also the spread of resistance. The prevention of pathogen host invasion by inhibiting bacterial virulence and biofilm formation, and the utilisation of bactericidal agents with different mode of action than classic antibiotics are the two most promising new alternative strategies to overcome antibiotic resistance. Based on these novel approaches, researchers are developing different advanced materials (nanoparticles, hydrogels and surface coatings) with novel antimicrobial properties. In this review, we summarise the recent advances in terms of engineered materials to prevent bacteria-resistant infections according to the antimicrobial strategies underlying their design.
... Эта угроза заставляет искать новые способы сохранения эффективности имеющихся антибиотиков [8]. Одним из таких подходов является использование так называемых «ассистентов антибиотиков»веществ, которые могут модифицировать чувствительность микроорганизмов к антибиотикам [9]. Мы полагаем, что потенциальными кандидатами на роль «ассистентов антибиотиков» могут быть метаболиты нормальной микрофлоры женского репродуктивного тракта. ...
Objective. Investigation of the influence of metabolites from the lactobacilli isolated from healthy women and LCR35 probiotic strain on sensitivity to antibiotics. Subject and methods. We studied the effects of H2O2, lactate, and surfactants obtained from 24 vaginal Lactobacillus spp. and metabolites from LCR35 on sensitivity to antibiotics of 172 strains of opportunistic bacteria. Results. H2O2 and surfactants but no lactic acid were more effective for increasing the sensitivity of bacteria to antibiotics. Strain LCR35 increased sensitivity to antibiotics of all test strains, to a greater extent – G. vaginalis, E. coli and Klebsiella spp. Conclusion. The phenomenon of potentiation of activity of antibiotic by metabolites from vaginal lactobacilli and LCR35 probiotic strain was detected. For effective treatment of inflammatory diseases by antibiotics should take into account the status of the normal microflora, and if necessary, compensate deficit by probiotic strains able to produce “assistants antibiotics”.
... Furthermore, the biofilm coating on a bacterial cell surface can serve as a protective shield against adverse extracellular environmental conditions [14,15], giving rise to more severe biofouling and corrosion of industrial equipment resulting from harsher cleansing methods in the routine cleaning process in the food industry [16]. Resistant strains adept at biofilm formation are hardly affected by traditional antibiotics and the evolution of bacterial antibiotic resistance has been much faster than the development of new antimicrobial agents [5,17], leading to the inevitable consequence that medicines might lose their potency over time [18]. Therefore, it is particularly imperative to recover the effectiveness of existing antibiotics to break down thick biofilm barriers and to overcome antibiotic resistance by efficient elimination of biofilms [13,19]. ...
The emergence of antibiotic resistance has resulted in an increasing difficulty treating clinical infections associated with biofilms formation, one of the key processes contributed to enhance antibiotic resistance in return. With the rapid development of nanotechnology, a new way to overcome antibiotic resistance was opened up. Based on multiple properties especially antibacterial potential of MoS2 nanosheets that have aroused wide attention, herein, a novel antimicrobial agent to combat resistant gram-positive Staphylococcus aureus (S. aureus) and gram-negative Salmonella was prepared using chitosan functionalized MoS2 nanosheets loading tetracycline hydrochloride drugs (abbreviated to CM-TH). The antibacterial and anti-biofilm activities of CM-TH nanocomposites expressed a synergy effect that the combination of nanomaterials and antibiotics were more efficient than both alone did. Particularly, the MIC values were generally decreased by a factor of dozens, suggesting CM-TH may become a possible alternative to traditional antibiotics in disrupting the biofilms and further to overcome antibiotic resistance in treating medical diseases.
... This danger forces to search for new ways to retain control of pathogens, which are based on the use of new agents, other than antibiotics or the creation of new strategies of the effective use of available antibiotics [5,32]. One of these strategies is the use of antibiotics in conjunction with the so-called antibiotic assistants-substances that can modify the sensitivity of microorganisms to antibiotics [34,46]. Metabolites of the normal microflora may be potential candidates for the role of Bassistants of antibiotics,^for example, the effectiveness of antibiotic treatment of sexually transmitted infections depends on the presence or absence of the normal microflora [31]. ...
We studied as hydrogen peroxide, lactic acid, or surfactants from clinical isolates of vaginal lactobacilli and cell-free supernatants from probiotic strain LCR35 can influence on the sensitivity of opportunistic bacteria to antibiotics. We found that the most effective in increasing sensitivity to antibiotics were hydrogen peroxide and surfactants or their combination but no lactic acid. In some cases, the effect of the composition of hydrogen peroxide and surfactants was clearly higher than the sum of effects of these substances alone. With using of the supernatant of LCR35 was shown that the combination of surfactant and lactate has greater effect compared with surfactants alone. In concluding, metabolites of vaginal lactobacilli are suitable for the role of "antibiotic assistants" and it can help solve the problems the antibiotic resistance.
... In addition, the techniques/ materials themselves require improvements to increase the materials' interfacial strength (for bulk GO) and to maximize the antibacterial/osteodifferentiation efficiencies (for rGO-PDA) toward clinical applications. By utilizing the chemical versatility of GO/PDA, the former is possible through the introduction of strong covalent cross-links ( Figure S7a), 58 whereas the latter can be fulfilled by surface decorating nanosilver, 27 antibiotics, 55 and osteogenic molecules 14,57 ( Figure S7b). Furthermore, it remains an important task to exploit the efficiency and safety in vivo, as well as to deepen the understanding of the structure−function correlations of graphene sheet surfaces. ...
To bring graphene of multifunctional nature out from its solution via facile self-assembly to form 2D surface nanostructures, with control over lateral size and surface properties, would be an intriguing subject, especially in biomedical fields where biointerfaces with function diversity are much demanded. Guided by this, we herein built such graphene-based self-assemblies on orthopedic titanium (Ti), attempting to selectively regulate bacterial activities and osteoblastic functions, which are both crucial in bone regeneration. Briefly, large-area graphene oxide (GO) sheets and functionalized, reduced GO (rGO) micro/nanosheets were self-assembled spontaneously and controllably onto solid Ti, via an evaporation-assisted, electrostatic assembly process and mussel-inspired one-pot assembling, respectively. The resultant layers were characterized in terms of topological structure, chemical composition, hydrophilicity, and protein adsorption properties. The assemblies' antibacterial efficacy was examined by challenging them with pathogenic Staphylococcus aureus (S. aureus) bacteria that produce biofilms, whereby around 50% anti-adhesion effects and considerable anti-biofilm activities were observed for both layer types, however, via plausibly dissimilar modes of action. Their cytocompatibility and osteogenic potential were also investigated. Interfaced with MC3T3-E1 cells, the functionalized rGO sheets evoked better cell adhesion and growth than GO sheets, while the latter elicited higher osteo-differentiation activity throughout a 28-d in vitro culture. In this work, we showed it is technically possible to construct graphene interface layers of varying lateral dimensions and surface properties, and proved the concept of using the obtained assemblies to address the two major challenges facing orthopedic clinics. Besides, we provided fundamental implications for understanding the surface-biology relationship of graphene biomaterials, in efforts to better design and more safely use them for future biomedicine.
Owing to its captivating properties, Graphene-based materials (GMBs) have appeared as a broad-spectrum antimicrobial material and attracting scientists and researchers’ attention. By focusing on the recent advances in the polymeric nanocomposite’s field, current study is positioned on the graphene-based polymeric composites having antibiofilm and antimicrobial activities to confront the current situations of microbial resistance against antibiotics and other drugs. Furthermore, this review summarizes the influence of different factors on the antimicrobial activities of graphene-based polymeric composites like size, shape, number of layers, concentration, dispersibility, and functionalization, and also shed the light on the possible mode of actions of these materials. Graphene-based polymeric composites exert its antimicrobial action by physical damages (e.g., direct sharp edges’ contact to cell membranes of bacteria, wrapping of the bacterial cell, phospholipid extraction, and photo-thermal ablation) and chemical damages (e.g. oxidative-stress and charge transfer). Besides, this review article thoroughly describes the antimicrobial applications of graphene-based polymeric composites, which are because of their good biocompatibility and superior antimicrobial properties such as wound bandages and dressings, antimicrobial coatings, drug delivery, food packaging, hydrogel formation, and water disinfection. Present review may stimulate major concerns, spur further developments, and provide valuable insight into the promising fields.
Antibiotic therapy is the most powerful strategy in treating bacterial infections in clinic. However, antibiotic resistance has become one of the biggest threats to public health worldwide due to the misuse and abuse of antibiotics. What is worse, the speed of the discovery of new antibiotics is largely hysteretic compared to that of the growth of antibiotic resistance. The conventional antibiotics are becoming less and less effective in killing bacteria and eradiating their biofilms, leading to increased medical costs, prolonged hospital stays, and higher mortality. The world is on the threshold of “post-antibiotic era”. Although various non-antibiotic strategies are developed to fight against antibiotic resistance, they are still far away from clinical applications owing to the systematic toxicity, physiological stability, in vivo feasibility, and so on. Antibiotic therapy is still irreplaceable and considered as the first choice in the fight against bacterial infections. Nanomaterials have shown great potential in restoring the antibacterial activity of conventional antibiotics by different kinds of mechanisms, including optimizing pharmacokinetics, improving antibiotic internalization, interfering bacterial metabolism, enhancing biofilm penetration, changing biofilm microenvironment, and so on. In this review, the recent strategies about improving the therapeutic efficacy of antibiotics to combat drug resistance using nanomaterials are summarized. The advantages and mechanisms of nanoparticle-based antibiotics are discussed as well.
The treatment of intracellular infections is very challenging given the ability of bacteria to “hide” inside the cells of the host, especially the ones of the immune system, thus hampering the action of many antimicrobial agents. The battle against these bacteria has been further exacerbated by the increasing diffusion of antimicrobial resistant strains. In this frame, nanoparticles (NPs) are a very promising strategy to overcome the limitations of free antimicrobial agents by administering them in an optimized manner.This PhD work, performed as part of the European Project ITN Cyclon Hit, aimed at the development and advanced characterisation of antibiotic-loaded biodegradable and biocompatible NPs made of poly (lactic acid) (PLA), poly (lactic-co-glycolic) (PLGA) and polycaprolactone (PCL) or of polymerised cyclodextrins (pCDs).The first two chapters are dedicated to the encapsulation of powerful but challenging drugs in polymeric NPs. Firstly, these carriers were employed for the simultaneous delivery of a potent drug combination recently discovered, ethionamide (ETH) and its booster, for tuberculosis therapy. Secondly, they were used to address the challenges related to the incorporation of a first-generation quinolone, pipemidic acid (PIP), with the aim of optimising its intracellular delivery in infections such as salmonellosis.The efficient co-incorporation of ETH and booster had to overcome several technological barriers. These drugs presented solubility, crystallisation and bioavailability-related problems which were overcome thanks to the developed NPs. Our engineered PLA and pCD NPs were both able to efficiently co-encapsulate the two molecules. Among the in depth-characterised formulations, pCDs NPs displayed the best physico-chemical properties and were shown to host the drugs both in the CD cavities and in confined spaces inside NPs crosslinked polymer. The pCD NPs were administered in vivo by endotracheal route directly to the infection site. Empty NPs were shown non-toxic after repeated pulmonary administration of high doses. Moreover, loaded pCD NPs led to a 3-log decrease in the pulmonary bacterial load of infected animals after only 6 administrations. Similarly, the incorporation of PIP faced challenges mainly related to PIP crystallization and burst release. Unfortunately, PIP displayed poor affinity for all the studied polymeric materials and its physical encapsulation was unsuccessful. Thus, an alternative approach was developed by coupling PIP to PCL by using an original catalyst-free drug-initiated reaction. The PCL-PIP conjugate self-assembled in NPs with up to 27 wt% PIP which were thoroughly characterised. However, the conjugate couldn’t be enzymatically degraded. With the design of novel PCL-PIP conjugates, this self-assembly approach could represent a promising strategy.The deep understanding of the structure and composition of complex core-corona nanocarriers containing one or two active molecules is crucial for their optimisation. The last two chapters are devoted to the innovative application of AFM-IR, an original nanospectroscopic method combining atomic force microscopy (AFM) with infrared (IR) spectroscopy, to the chemical analysis of PLGA NPs or to their label-free detection after cell internalisation.AFM-IR is able to provide chemical characterisation at the nanometer scale (resolution ~10nm). One main breakthrough here is the application of the recently developed tapping mode allowing the investigation of single polymeric NPs. The specific IR signal of NPs constituents was used to unravel the chemical composition of their core and corona as well as to precisely locate the drug. Moreover, the AFM-IR in contact mode enabled for the first time the label-free localisation and unambiguous chemical identification of NPs inside cells using the polymer IR specific response as a fingerprint. This work paves the way for countless application of this technique in the field of drug delivery.
AFM-IR is a photothermal technique which combines AFM and infrared (IR) spectroscopy to unambiguously identify the chemical composition of a sample with tens of nanometer spatial resolution. So far, it was successfully used in contact mode in a variety of applications. However, contact mode is unsuitable for soft or loosely-adhesive samples such as polymeric nanoparticles (NPs) of less than 200 nm of wide interest for biomedical applications. We describe here the theoretical basis of the innovative tapping-AFMIR mode that can address novel challenges in imaging and chemical mapping. The new method enables gaining information not only on NP morphology and composition, but also revealed drug location and core-shell structures. If up to now the locations of NP components could only be hypothesized, tapping AFM-IR allows to accurately visualizing both the location of the NPs’ shells and of the incorporated drug, pipemidic acid. The preferential accumulation of the drug in the NPs’ top layers is proved, despite its low concentration (<1 wt%). These studies pave the way towards the use of tapping AFM-IR as a powerful tool to control the quality of NP formulations based on individual NP detection and component quantification.
Ampicillin is a one of effective antibiotics against Gram-positive and Gram-negative bacteria. The present study aims to label ampicillin loaded graphene oxide nanoflake (AMP-GO) with 99mTc and evaluate of its in vitro binding to S. aureus and E. coli. Firstly, ampicillin was loaded onto graphene oxide nanoflake prepared. AMP-GO was characterized by Fourier Transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscope (SEM) techniques, and the amount of loaded ampicillin onto GO was determined by UV-Vis absorption spectroscopy. AMP and AMP-GO were labeled with 99mTc using stannous chloride reducing agent. Labeling efficiency of 99mTc-AMP-GO was found to be 97.66±2.06%. 99mTc-AMP-GO has higher binding efficiencies to both S. aureus and E. coli than 99mTc-AMP. 99mTc-AMP-GO could be promising candidate as agent infection nuclear imaging. Furthermore in vivo studies of 99mTc-AMP-GO with infected rats are planned to be done. This article is protected by copyright. All rights reserved.
The application of ultrasonic irradiation for the activation of chemical reactions, commonly known as sonochemistry, has contributed to the development of a number of processes that are considered to be environmentally benign. The use of ultrasonic waves to activate synthetic processes usually results in shorter reaction times and higher yields and selectivities, namely, cleaner products. This work aims to provide an overview of recent applications that illustrate the use of sonochemistry in the field of green or sustainable synthesis. In the first part of the chapter, organic synthetic processes are surveyed, including applications in aqueous, nonaqueous, or biphasic systems as well as homogeneous and heterogeneous catalytic reactions. In the second part of the work, the focus will be on an emerging field, the preparation of nanoparticles.
Antimicrobial nanomaterials for water treatment have attracted ever-growing research attention as they provide alternative approaches for disinfection and microbial control. Among all the antimicrobial nanomaterials, graphene-based nanomaterials have emerged recently. This review article seeks to provide a whole view on graphene-based antimicrobial nanomaterials particularly applied for water disinfection and pathogenic microorganism control. Herein, we firstly give a brief introduction of the antimicrobial characters of single-component graphene materials. In the following section, the functionalization of graphene with metal nanoparticles, photocatalysts, polymers and biocidal compounds for tailorable antimicrobial activities and microbial inactivation are thoroughly reviewed.In addition, innovative devices (hydrogel, thin film, composite membrane, recoverable nanocomposites and electrode) assembled by graphene-based nanomaterials used for water disinfection and microbial control are discussed in detail. Finally, the future opportunities and challanges of designing graphene-based antimicrobial nanomaterials for water disinfection are addressed.
Conjugation of two or more substances to enhance the antibacterial properties of the resulting hybrids can be a useful method to fight bacterial resistance. In this work, a series of ligands composed of two Quaternary ammonium compounds (QAC) and chromene parts synthesized and then assembled on surfaces of graphene oxide (GO) and reduced graphene oxide (rGO). The formation of hybrids is caused by π-π interactions between GO/rGO and chromene part of ligands in addition to electrostatic interactions. The primary ligands only had an impact on Gram-positive and didn't exhibit activity against Gram-negative bacteria while the new hybrids showed increased effect on Gram-positive bacteria, also have a significant effect against Gram-negative bacteria.
A global upsurge of antibiotic resistance has led to the research of metal-based antimicrobial therapy. Nonetheless, the clinical translation of metal oxides is often hampered by their poor aqueous solubility. This work unravels a surfactant-free synthesis of a water-soluble PEGylated nanographene oxide/zinc-doped copper oxide complex (NGO-PEG-Zn-CuO). A simple, one-step sonochemical technique is employed to deposit Zn-CuO nanoparticles (NPs) on NGO-PEG. This complex demonstrates excellent aqueous solubility in different physiological solutions, including serum. Moreover, it exhibits excellent stability in water for a period of more than two months. We uncover its mechanism of cell death (E. coli and S. aureus) associated with oxidative stress and high production of reactive oxygen species (ROS) compared to NGO-ZnCuO, ZnCuO and NGO-PEG. These results not only show the superior potency of the NGO-PEG-ZnCuO complex over NGO-ZnCuO, ZnCuO and NGO-PEG, and the behavior of ROS in their antimicrobial efficacy but also almost no cytotoxicity exerted by these complexes on cultured HeLa cells.
We report on a simple and effective ultrasound-assisted deposition of vanillin nanoparticles (∼50nm in size), raspberry ketone (RK) nanoparticles (∼40nm in size) and camphor nanoparticles (width ∼30nm, length ∼40nm in size) on textiles and on polypropylene surfaces. The excellent antibacterial and antifungal activity of the fragrant coatings on cotton bandages, and polypropylene surface against Escherichia coli (E. coli), Salmonella paratyphi A (S. paratyphi A) and the yeast Candida albicans (C. albicans) cultures was demonstrated. It is worth pointing out that these fragrant materials are edible, making them very useful for packaging. The mechanism of the edible fragrant coating formation and adhesion to the textile was discussed, and finally an up-scaling of the sonochemical process for textile coating was carried out.
This review focuses on the development of nanoparticle systems that enables to enhance and restore the antibiotic activity for drug-resistant organisms. New and more aggressive antibiotic resistant bacteria and parasites calls for the development of new therapeutic strategies to overcome the inefficiency of conventional antibiotics and bypass treatment limitations related to these pathologies. Nanostructured biomaterials, nanoparticles in particular, have unique physicochemical properties such as ultra-small and controllable size, large surface area to mass ratio, high reactivity, and functionalizable structure. These properties can be applied to facilitate the administration of antimicrobial drugs, thereby overcoming some of the limitations in traditional antimicrobial therapeutics. Here the current progress and challenges in synthesizing nanoparticle platforms for restoring activity of various antimicrobial drugs are reviewed with an emphasis on antibiotics. We also call attention to the need to unite the shared interest between nanoengineers and microbiologists in developing nanotechnology for the treatment of microbial diseases.
Photodynamic therapy is widely used in clinics and for anti-bacterial applications. The major challenge is the limited depth of tissue penetration of light and poor targetability. In this study, magnetite nanoparticles were used as a highly sensitive T2-weighted MR imaging contrast agents to target the tumor and mimic horseradish peroxidase (HRP), which could catalyze the decomposition of hydrogen peroxide to generate reactive oxygen species (ROS) to inhibit the tumor in vivo. In these experiments, MNPs were demonstrated to possess the enzyme-mimicking activity in different pH values, and the activity was dependent on the size of the MNPs: the smaller the size, the higher the activity. We demonstrated that MNPs showed highly efficient anti-bacterial (E. coli) activity in presence of H2O2. The E. coli inhibition ratio reached nearly 100% at optimal concentration. The anti-tumor activity was evaluated through HeLa cell viability under treatment with MNPs and H2O2. Consequently, the cell viability was significantly decreased and more than 80% of HeLa cells were dead after treatment with MNPs and H2O2 under different pH values. MR imaging was used to demonstrate the tumor targetability of 13 nm MNPs in vitro and in vivo. Consequently, the relaxivity of the 13 nm MNPs was determined to be r2 = 104 s−1 mM−1. The MR signal was much more negative and the intensity was significantly diminished with the increase of the concentration of 13 nm MNPs in vitro. The tumor signal was clearly visualized and a 3-fold decrease of the MR signal intensity of the tumor site of the mice was observed after 24 h-post treatment with the 13 nm MNPs. Finally, the tumor inhibition in vivo was investigated using 6 nm MNPs in BALB/c nude female mice bearing subcutaneously implanted HeLa cells on the right flank. The results show statistically significant efficacy in delaying tumor growth from day 6, and an approximately 99% tumor inhibition ratio was shown by the combination of MNPs and H2O2 after treatment for 17 days. By leveraging the passive targeting and MR imaging properties, we expect that the enzyme-mimicking MNPs could be used for cancer theranostics and may open up a new avenue for the treatment of epidermal infections.
The treatment of bacterial infection is one of the most challenging tasks in the biomedical field. Antibiotics have been developed over 70 years and are regarded as the most efficient type of drug to treat bacterial infection. However, there is a concern that the overuse of antibiotics can lead to a growing number of multidrug resistant bacteria. The development of antibiotic delivery systems to improve the biodistribution and bioavailability of antibiotics is a practical strategy for reducing the generation of antibiotic-resistance and increasing the lifespan of newly developed antibiotics. Here we present antibiotic delivery system (Van⊂SGNPs@RBC) based on core-shell supramolecular gelatin nanoparticles (SGNPs) for adaptive and "on-demand" antibiotic delivery. The core composed of cross-linked SGNPs allows for bacterial infection-microenvironment responsive release of antibiotics. The shell coated with uniformed red blood cell membranes executes the function of disguise for reducing the clearance by immune system during the antibiotic delivery, as well as absorbs the bacteria exotoxin for relieving symptoms caused by bacterial infection. This approach demonstrates an innovative and biomimetic antibiotic delivery system for the treatment of bacterial infection with minimum dose of antibiotics.
Graphene oxide (GO) nanoparticle is a high potential effective absorbent. Tetracycline (TC) is a broad-spectrum antibiotic produced, indicated for use against many bacterial infections. In the present research, a systematic study of the adsorption and release process of tetracycline on GO was performed by varying pH, sorption time and temperature. The results of our studies showed that tetracycline strongly loads on the GO surface via π-π interaction and cation-π bonding. Investigation of TC adsorption kinetics showed that the equilibrium was reached within 15 min following the pseudo-second-order model with observed rate constants of k2 = 0.2742-0.5362 g/mg min (at different temperatures). The sorption data has interpreted by the Langmuir model with the maximum adsorption of 323 mg/g (298 K). The mean energy of adsorption was determined 1.83 kJ/mol (298 K) based on the Dubinin-Radushkevich (D-R) adsorption isotherm. Moreover, the thermodynamic parameters such as ΔH°, ΔS° and ΔG° values for the adsorption were estimated which indicated the endothermic and spontaneous nature of the sorption process. The electrochemistry approved an ideal reaction for the adsorption under electrodic process. Simulation of GO and TC was done by LAMMPS. Force studies in z direction showed that tetracycline comes close to GO sheet by C8 direction. Then it goes far and turns and again comes close from amine group to the GO sheet.
Bacterial spot caused by Xanthomonas perforans is a major disease of tomatoes, leading to reduction in production by 10-50%. While copper (Cu)-based bactericides have been used for disease management, most of the X. perforans strains isolated from tomatoes in Florida and other locations worldwide are Cu-resistant. We have developed DNA-directed silver (Ag) nanoparticles (NPs) grown on graphene oxide (GO). These Ag@dsDNA@GO composites effectively decrease X. perforans cell viability in culture and on plants. At the very low concentration of 16 ppm of Ag@dsDNA@GO, composites show excellent antibacterial capability in culture with significant advantages in improved stability, enhanced antibacterial activity and stronger adsorption properties. Application of Ag@dsDNA@GO at 100 ppm on tomato transplants in a greenhouse experiment significantly reduced the severity of bacterial spot disease compared to untreated plants, giving results similar to those of the current grower standard treatment, with no phytotoxicity.
Nanotechnology is providing new ways to manipulate the structure and chemistry of surfaces to inhibit bacterial colonization. In this study, we evaluated the ability of glass slides coated with zinc oxide (ZnO) nanoparticles to restrict the biofilm formation of common bacterial pathogens. The generation of hydroxyl radicals, originating from the coated surface, was found to play a key role in antibiofilm activity. Furthermore, we evaluated the ability of the nanoparticle coating to enhance the antibacterial activity of commonly-used antibiotics. The ZnOnanoparticles were synthesized and deposited on the surface of glass slides using a one-step ultrasound irradiation process. Several physico-chemical surface characterization methods were performed to prove the long-term stability and homogenity of the coated films. Collectively, our findings may open a new door for utilizing ZnOnanoparticle films as antibiofilm coating of surfaces, thus providing a versatile platform for a wide range of applications both in medical and industrial settings, all of which are prone to bacterial colonization.
Using high-intensity ultrasound, in situ generated α-amylase nanoparticles (NPs) were immobilized on polyethylene (PE) films. The α-amylase NP-coated PE films have been characterized by E-SEM, FTIR, DLS, XPS and RBS. The PE was reacted with HNO(3) and NPs of the α-amylase were also deposited on the activated PE. The PE impregnated with α-amylase (4μg per 1mg PE) was used for hydrolyzing soluble potato starch to maltose. The immobilization improved the catalytic activity of α-amylase at all the reaction conditions studied. The kinetic parameters, K(m) (5 and 4gL(-1) for the regular and activated PE, respectively) and V(max) (5×10(-7)molml(-1)min(-1), almost the same numbers were obtained for the regular and activated PEs) for the immobilized amylase were found to slightly favor the respective values obtained for the free enzyme (K(m)=6.6gL(-1), V(max)=3.7×10(-7)molml(-1)min(-1)). The enzyme remained bound to PE even after soaking the PE in a starch solution for 72h and was still found to be weakly active.
This work describes a general method for the preparation of salt nanoparticles (NPs) made from an aqueous solution of ionic compounds (NaCl, CuSO(4) and KI). These nanoparticles were created by the application of ultrasonic waves to the aqueous solutions of these salts. When the sonication was carried out in the presence of a glass microscope slide, a parylene-coated glass slide, or a silicon wafer the ionic NPs were embedded in these substrates by a one-step, ultrasound-assisted procedure. Optimization of the coating process resulted in homogeneous distributions of nanocrystals, 30 nm in size, on the surfaces of the substrates. The morphology and structure of each of the coatings were characterized by physical and chemical methods, such as X-ray diffraction (XRD), scanning electron microscopy (SEM), atomic force microscopy (AFM), Raman spectroscopy and X-ray photoelectron spectroscopy (XPS). After 24 h of leaching into water the nanoparticles of the inorganic salts were still present on the slides, and complete leaching of nanoparticles occurred only after 96 h. A mechanism of the ultrasound-assisted coating is proposed.
Facilely synthesized cationic peptidopolysaccharides, which have a bacterial peptidoglycan-mimetic structure, show outstanding broad-spectrum activities against clinically significant bacteria and fungi and low mammalian cytotoxicity. Their structural affinity with microbial cell-wall constituents promotes penetration to reach the cytoplasmic membrane resulting in excellent antimicrobial activity and high selectivity.
The ability of bacteria to colonize catheters is a major cause of infection. In the current study, catheters were surface-modified with MgF2 nanoparticles (NPs) using a sonochemical synthesis protocol described previously. The one-step synthesis and coating procedure yielded a homogenous MgF2 NP layer on both the inside and outside of the catheter, as analyzed by high resolution scanning electron microscopy and energy dispersive spectroscopy. The coating thickness varied from approximately 750 nm to 1000 nm on the inner walls and from approximately 450 nm to approximately 580 nm for the outer wall. The coating consisted of spherical MgF2 NPs with an average diameter of approximately 25 nm. These MgF2 NP-modified catheters were investigated for their ability to restrict bacterial biofilm formation. Two bacterial strains most commonly associated with catheter infections, Escherichia coli and Staphylococcus aureus, were cultured in tryptic soy broth, artificial urine and human plasma on the modified catheters. The MgF2 NP-coated catheters were able to significantly reduce bacterial colonization for a period of 1 week compared to the uncoated control. Finally, the potential cytotoxicity of MgF2 NPs was also evaluated using human and mammalian cell lines and no significant reduction in the mitochondrial metabolism was observed. Taken together, our results indicate that the surface modification of catheters with MgF2 NPs can be effective in preventing bacterial colonization and can provide catheters with long-lasting self-sterilizing properties.
The treatment and prevention of infectious diseases is a major part of both clinical and investigative medicine. As the use of conventional antibiotics rises, antimicrobial resistance patterns develop, necessitating the continuous need for newer and more effective therapies. Nanotechnology, defined as the production and application of materials in the nanoscale range (1-100 nm), has been the focus of several investigations as a result of unique physical and chemical properties of nanomaterials. . Specifically, nanomaterials provide added benefits due to their small size; allowing for an increased ability to surpass most physiologic barriers and reach their intended targets, and high surface area-to-volume ratio, allowing for increased potential to interact with pathogen membranes and cell walls. This review focuses of the potential therapeutic and preventative applications of nanotechnology-based drug delivery systems in infectious disease.
Two-dimensional graphene offers interesting electronic, thermal, and mechanical properties that are currently being explored for advanced electronics, membranes, and composites. Here we synthesize and explore the biological applications of nano-graphene oxide (NGO), i.e., single-layer graphene oxide sheets down to a few nanometers in lateral width. We develop functionalization chemistry in order to impart solubility and compatibility of NGO in biological environments. We obtain size separated pegylated NGO sheets that are soluble in buffers and serum without agglomeration. The NGO sheets are found to be photoluminescent in the visible and infrared regions. The intrinsic photoluminescence (PL) of NGO is used for live cell imaging in the near-infrared (NIR) with little background. We found that simple physisorption via pi-stacking can be used for loading doxorubicin, a widely used cancer drug onto NGO functionalized with antibody for selective killing of cancer cells in vitro. Owing to its small size, intrinsic optical properties, large specific surface area, low cost, and useful non-covalent interactions with aromatic drug molecules, NGO is a promising new material for biological and medical applications.
We demonstrated that the individual graphene oxide sheets can be readily reduced under a mild condition using L-ascorbic acid (L-AA). This simple approach should find practical applications in large scale production of water soluble graphene.
The spread of antibiotic-resistant bacteria and parasites calls for the development of new therapeutic strategies with could potentially reverse this trend. Here, a proposal is presented to exploit a sonochemical method to restore the antibiotic activity of tetracycline (TTCL) against resistant bacteria by converting the antibiotic into a nanoparticulate form. The demonstrated sonochemical method allows nanoscale TTCL assembly to be driven by supramolecular hydrogen bond formation, with no further modification to the antibiotic's chemical structure. It is shown that tetracycline nanoparticles (TTCL NPs) can act as antibacterial agents, both against TTCL sensitive and against resistant bacterial strains. Moreover, the synthesized antibiotic nanoparticles (NPs) can act as effective gene-silencing agents through the use of a TTCL repressor in Trypanosome brucei parasites. It is demonstrated that the NPs are nontoxic to human cells and T. brucei parasites and are able to release their monomer components in an active form in a manner that results in enhanced antimicrobial activity relative to a homogeneous solution of the precursor monomer. As the TTCL NPs are biocompatible and biodegradable, sonochemical formation of TTCL NPs represents a new promising approach for generation of pharmaceutically active nanomaterials.
In the present work nanoparticles (NPs) of pepsin were generated in an aqueous solution using high-intensity ultrasound, and were subsequently immobilized on low-density polyethylene (PE) films, or on polycarbonate (PC) plates, or on microscope glass slides. The pepsin NPs coated on the solid surfaces have been characterized by HRSEM, TEM, FTIR, XPS and DLS. The amount of enzyme introduced on the substrates, the leaching properties, and the catalytic activity of the immobilized enzyme on the three surfaces are compared. Catalytic activities of pepsin deposited onto the three solid surfaces as well as free pepsin, without sonication, and free pepsin NPs were compared at various pH levels and temperatures using a hemoglobin assay. Compared to native pepsin, pepsin coated onto PE showed the best catalytic activity in all the examined parameters. Pepsin immobilized on glass exhibited better activity than the native enzyme, especially at high temperatures. Enzyme activity of pepsin immobilized on PC was no better than native enzyme activity at all temperatures at pH = 2, and only over a narrow pH range at 37 0C was the activity improved over the native enzyme. A remarkable observation is that immobilized pepsin on all the surfaces was still active to some extent even at pH = 7, while free pepsin was completely inactive. The kinetic parameters, Km and Vmax were also calculated and compared for all the samples. Relative to the free enzyme, pepsin coated PE showed the greatest improvement in kinetic parameters (Km= 15 g/L, Vmax= 719 U/mg versus Km= 12.6 g/L and Vmax= 787 U/mg, respectively), whereas pepsin coated on PC exhibited the most unfavorable kinetic parameters (Km= 18 g/L, Vmax= 685 U/mg). The values for the anchored enzyme-glass were Km= 19 g/L, Vmax = 763 U/mg.
The objective of this study was to fabricate injectable calcium sulfate bone cement beads loaded with an antibiotic nanoformulation, capable of delivering antibiotic locally to confirm antibacterial activity.
Tetracycline nanoparticles (Tet NPs) were prepared using an ionic gelation method and characterized using DLS, SEM, and FTIR to determine certain factors such as size, morphology, stability and chemical interaction of the drug with the polymer. Further, calcium sulfate (CaSO4) control and CaSO4-Tet NP composite beads were prepared and characterized using SEM, FTIR and XRD. The drug release pattern, material properties and antibacterial activity were evaluated. In addition, protein adsorption, cytocompatibility and alkaline phosphatase activity of the CaSO4-Tet NP composite beads in comparison to the CaSO4 control were analyzed.
Tet NPs showed a size range of 130±20nm and the entrapment efficiency calculated was 89%. The composite beads showed sustained drug release pattern. Further the drug release data was fitted into various kinetic models wherein the Higuchi model showed higher correlation value (R(2)=0.9279) as compared to the other models. The composite beads showed antibacterial activity against Streptococcus aureus and Escherichia coli. The presence of Tet NPs in the composite bead didn't alter its cytocompatibility. In addition, the composite beads enhanced the ALP activity of hPDL cells.
The antibacterial and cytocompatible CaSO4-Tet NP composite beads could be beneficial in periodontal management to reduce the bacterial load at the infection site.
Tet NPs would deliver antibiotic locally at the infection site and the calcium sulfate cement, would itself facilitate tissue regeneration.
Despite the current advancement in drug discovery and pharmaceutical biotechnology, infection diseases induced by bacteria continue to be one of the greatest health problems worldwide, afflicting millions of people annually. Almost all microorganisms have, in fact, an intrinsic outstanding ability to flout many therapeutic interventions, thanks to their fast and easy-to-occur evolutionary genetic mechanisms. At the same time, big pharmaceutical companies are losing interest in new antibiotics development, shifting their capital investments in much more profitable research and development fields. New smart solutions are, thus, required to overcome such concerns, and should combine the feasibility of industrial production processes with cheapness and effectiveness. In this framework, nanotechnology-based solutions, and in particular silver nanoparticles (AgNPs), have recently emerged as promising candidates in the market as new antibacterial agents. AgNPs display, in fact, enhanced broad-range antibacterial/antiviral properties, and their synthesis procedures are quite cost effective. However, despite their increasing impact on the market, many relevant issues are still open. These include the molecular mechanisms governing the AgNPs-bacteria interactions, the physico-chemical parameters underlying their toxicity to prokaryotes, the lack of standardized methods and materials, and the uncertainty in the definition of general strategies to develop smart antibacterial drugs and devices based on nanosilver. In this review, we analyze the experimental data on the bactericidal effects of AgNPs, discussing the complex scenario and presenting the potential drawbacks and limitations in the techniques and methods employed. Moreover, after analyzing in depth the main mechanisms involved, we provide some general strategies/procedures to perform antibacterial tests of AgNPs, and propose some general guidelines for the design of antibacterial nanosystems and devices based on silver/nanosilver.
Rapid, reliable recognition and detection of bacteria from an authentic specimen have been gained increasing interests in the past decades. Various materials have been designed and prepared for implementation of bacterial recognition and treatment in the artificial systems. However, in the complicated physiological condition, the macrophages always compromise the outcomes of bacterial detection and/or treatment. In this work, we demonstrated the vancomycin-modified mesoporous silica nanoparticles (MSNsVan) for efficiently targeting and killing gram-positive bacteria over macrophage-like cells. Owing to the specific hydrogen bonding interactions of vancomycin towards the terminal D-alanyl-D-alanine moieties of gram-positive bacteria, the MSNsVan exhibited enhanced recognition for gram-positive bacteria due to the multivalent hydrogen binding effect. Furthermore, the fluorescent molecules (FITC) were covalently decorated inside of mesopores of MSNs for tracking and visualizing the MSNsVan during the detection/treatment processes. Upon incubation of FITC decorated MSNs with bacteria (i.e., S. aureus and E. coli as gram-positive and gram-negative bacteria, respectively) or macrophage-like cells (Raw 264.7), the fluorescence signals in S. aureus were 2~4 times higher than that in E. coli and no detectable fluorescence signals were observed in Raw 264.7 cells under the same condition. Finally, the MSNsVan showed unambiguous antibacterial efficacy without decrease in cell viability of macrophage-like cells. This new strategy opens a new door for specific detection and treatment of pathogenic bacteria with minimized side effect.
A series of vitamin E-containing biodegradable antimicrobial cationic polycarbonates is designed and synthesized via controlled organocatalytic ring-opening polymerization. The incorporation of vitamin E significantly enhances antimicrobial activity. These polymers demonstrate broad-spectrum antimicrobial activity against various microbes, e.g., S. aureus (Gram-positive), E-coli (Gram-negative) and C. albicans (fungi). More importantly, the co-delivery of such polymers with selected antibiotics (e.g., doxycycline) shows high synergism towards difficult-to-kill bacteria P. aeruginosa. These findings suggest that these vitamin E-functionalized polycarbonates are potentially useful antimicrobial agents against challenging bacterial/fungal infections.
Drug delivery systems improve the therapeutic efficacy and safety of drugs by delivering them at a controlled rate depending on the body requirements and the site of action. These systems aid in reducing the amount of drug required, the number of doses, side effects, and bioinactivation. Currently, delivery systems for drug targeting and controlled release are being developed using drug nanoparticles. Several techniques, such as spray drying and milling, have been used in the past for the manufacture of drug nanoparticles, but these methods have several disadvan-tages. Supercritical fluid technologies such as RESS and SAS do provide novel methods for particle formation, but in most cases, they still cannot produce particles in the nanometer range (<300 nm) necessary for drug targeting and controlled release. In this work, we propose a technique that can produce drug particles in the nanometer range with a narrow size distribution. This new technique is a modification of the currently existing SAS technique and involves the use of a vibrating surface that atomizes the jet into microdroplets. The ultrasonic field generated by the vibrating surface also enhances mass transfer through increased mixing. The new technique is demonstrated for the production of tetracycline nanoparticles as small as 125 nm in size with a narrow size distribution. Particle sizes are easily controlled using this technique by changing the vibrational intensity of the vibrating surface.
Zinc-doped copper oxide nanoparticles are synthesized and simultaneously deposited on cotton fabric using ultrasound irradiation. The optimization of the processing conditions, the specific reagent ratio, and the precursor concentration results in the formation of uniform nanoparticles with an average size of ≈30 nm. The antibacterial activity of the Zn-doped CuO Cu0.88 Zn0.12 O in a colloidal suspension or deposited on the fabric is tested against Escherichia coli (Gram negative) and Staphylococcus aureus (Gram positive) bacteria. A substantial enhancement of 10 000 times in the antimicrobial activity of the Zn-CuO nanocomposite compared to the pure CuO and ZnO nanoparticles (NPs) is observed after 10 min exposure to the bacteria. Similar activities are observed against multidrug-resistant bacteria (MDR), (i.e., Methicillin-resistant S. aureus and MDR E. coli) further emphasizing the efficacy of this composite. Finally, the mechanism for this enhanced antibacterial activity is presented.
Despite the fact that pathogenic infections are widely treated by antibiotics in the clinic nowadays, the increasing risk of multidrug-resistance associated with abuse of antibiotics is becoming a major concern in global public health. The increased death toll caused by pathogenic bacterial infection calls for effective antibiotic alternatives. Lysozyme-coated mesoporous silica nanoparticles (MSNs⊂Lys) are reported as antibacterial agents that exhibit efficient antibacterial activity both in vitro and in vivo with low cytotoxicity and negligible hemolytic side effect. The Lys corona provides multivalent interaction between MSNs⊂Lys and bacterial walls and consequently raises the local concentration of Lys on the surface of cell walls, which promotes hydrolysis of peptidoglycans and increases membrane-perturbation abilities. The minimal inhibition concentration (MIC) of MSNs⊂Lys is fivefold lower than that of free Lys in vitro. The antibacterial efficacy of MSNs⊂Lys is evaluated in vivo by using an intestine-infected mouse model. Experimental results indicate that the number of bacteria surviving in the colon is three orders of magnitude lower than in the untreated group. These natural antibacterial enzyme-modified nanoparticles open up a new avenue for design and synthesis of next-generation antibacterial agents as alternatives to antibiotics.
Conventional antibiotic therapies are becoming less efficient owing to the emergence of antibiotic-resistance bacterial strains. Development of novel antibacterial material to effectively inhibit or kill bacteria is crucial. A graphene based photothermal agent, magnetic reduced graphene oxide functionalized with glutaraldehyde (MRGOGA), was synthesized for efficient capture and effective killing of both gram-positive Staphylococcus aureus (S. aureus) and gram-negative Escherichia coli (E. coli) bacteria upon NIR laser irradiation. In the present work, we took advantage of the excellent photothermal properties of RGO upon NIR laser irradiation and glutaraldehyde as an efficient capturing agent towards both bacteria. Its magnetic characteristic facilitates the captured bacteria be readily trapped in a small volume by the external magnet. The synergetic effects increase the heating extent by MRGOGA upon NIR laser irradiation and the killing of the captured bacteria. The survival rate and membrane-integrity assay demonstrates that 80 ppm MRGOGA solution provided rapid and effective killing of up to 99% of both gram-positive and gram-negative bacteria in ten min upon NIR laser irradiation under batch operation mode. Graphene demonstrated better photothermal antibacterial efficiency than carbon nanotubes. Furthermore, a microfluidic chip system under continuous operation mode demonstrates the re-usability of MRGOGA and offers a biocompatible platform for on-line phothothermal sterilization.
The use of nanoscale materials as bactericidal agents represents a novel paradigm in the development of therapeutics against drug-resistant pathogenic bacteria. In this paper the antimicrobial activity of a water soluble (gold nanoparticle)-polythiophene (AuNP-PTh) composite against common bacterial pathogens is reported. The nanocomposite is broad-spectrum in its bactericidal activity and exhibits a membrane-directed mode of action on target pathogens. The therapeutic potency of AuNP-PTh is demonstrated by experiments which reveal that the nanocomposite can breach the outer membrane defense barrier of Gram-negative pathogens for subsequent killing by a hydrophobic antibiotic, inhibit the growth of model gastrointestinal pathogens in simulated gastric fluid, and significantly eradicate bacterial biofilms. The high bacterial selectivity and lack of cytotoxicity on human cells augers well for future therapeutic application of the nanocomposite against clinically relevant pathogenic bacteria.
Antimicrobial silver particles are created on calcium phosphate (CaP) biomaterials by sequentially incubating in citric acid and silver nitrate solutions. The subsequent silver release kinetics and released dosage are controlled by simply changing the solution conditions during growth of silver particles. Released silver efficiently suppresses the growth of gram-positive Staphylococcus aureus and gram-negative Escherichia coli without significant cytotoxicity to eukaryotic cells.
AMORPHOUS metallic alloys ('metallic glasses') lack long-range crystalline order and have unique electronic, magnetic and corrosion-resistant properties1–3. Their applications include use in power-transformer cores, magnetic storage media, cryothermometry and corrosion-resistant coatings. The production of metallic glasses is made difficult, however, by the extremely rapid cooling from the melt that is necessary to prevent crystallization. Cooling rates of about 105 to 107 K s−1 are generally required; for comparison, plunging red-hot steel into water produces cooling rates of only about 2,500 K s−1. Metallic glasses can be formed by splattering molten metal on a cold surface using techniques such as gun, roller or splat quenching4,5. Acoustic cavitation is known to induce extreme local heating in otherwise cold liquids, and to provide very rapid cooling rates6–11. Here we describe the synthesis of metallic-glass powders using the microscopically extreme (yet macroscopically mild) conditions induced by high-intensity ultrasound. The sonolysis of iron pentacarbonyl, a volatile organometallic compound, produces nearly pure amorphous iron. This amorphous iron powder is a highly active catalyst for the Fischer–Tropsch hydrogenation of carbon monoxide and for hydrogenolysis and dehydrogenation of saturated hydrocarbons.
A facile sonochemical route for the synthesis of graphene nanosheets via reduction of graphene oxide (GO) has been reported. The synthesized graphene sheets are characterized using UV-vis spectra, Fourier transform infra-red (FT-IR) spectra, transmission electron microscope, X-ray photoelectron spectra (XPS) and Raman spectroscopic techniques. The UV-vis spectroscopy results showed that the absorption peak was red shifted due to the reduction of GO into graphene. FT-IR and XPS spectra revealed the removal of oxygenated functional groups in graphene after the reduction process. Raman spectra confirmed the restoration of new sp(2) carbon domains in graphene sheets after the reduction. The sonochemical approach for the synthesis of graphene nanosheets is relatively fast, cost-effective and efficient as compared to other methods.
The electrochemical properties of graphene paper electrodes used in lithium batteries were reported. Scanning electron microscopy (SEM) studies of graphene paper show that it possesses a layered structure through the entire cross section. Cyclic voltammograms using graphene paper and graphite as electrodes in 1.0 M LiPF6 with Li as the counter and reference electrodes reveal a much higher specific cathodic current with graphene paper compared to graphite as the electrode. The strong, sharp peak at 1.47 V show that more active intercalation sites are available in graphene paper, which is found to be due to lithium interactions with the residual oxygen-containing functional groups within graphene nanosheets. Using the graphite electrode, the discharge capacity is found to be 298 mA h g-1, decreasing to 240 mA h g-1 after 50 cycles.
Dual-function poly(L-lysine) (PLL) composites that function as antibacterial agents and promote the growth of human cell culture have been sought by researchers for a long period. In this paper, we report the preparation of new graphene derivative-PLL composites via electrostatic interactions and covalent bonding between graphene derivatives and PLL. The resulting composites were characterized by infrared spectroscopy, scanning electron microscopy, and X-ray photoelectron spectroscopy. The novel dual function of PLL composites, specifically antibacterial activity and biocompatibility with human cells [human adipose-derived stem cells and non-small-cell lung carcinoma cells (A549)], was carefully investigated. Graphene-DS-PLL composites composed of 4-carboxylic acid benzene diazonium salt (DS) generated more anionic carboxylic acid groups to bind to cationic PLLs, forming the most potent antibacterial agent among PLL and PLL composites with high biocompatibility with human cell culture. This dual functionality can be used to inhibit bacterial growth while enhancing human cell growth.
The design of polyelectrolyte multilayers (PEMs) that can be prefabricated on an elastomeric stamp and mechanically transferred onto biomedically-relevant soft materials, including medical-grade silicone elastomers (E’∼450–1500 kPa; E’-elastic modulus) and the dermis of cadaver skin (E’∼200–600 kPa), is reported. Whereas initial attempts to stamp PEMs formed from poly(allylamine hydrochloride) and poly(acrylic acid) resulted in minimal transfer onto soft materials, we report that integration of micrometer-sized beads into the PEMs (thicknesses of 6–160 nm) led to their quantitative transfer within 30 seconds of contact at a pressure of ∼196 kPa. To demonstrate the utility of this approach, PEMs were impregnated with a range of loadings of silver-nanoparticles and stamped onto the dermis of human cadaver skin (a wound-simulant) that was subsequently incubated with bacterial cultures. Skin dermis stamped with PEMs that released 0.25 ± 0.01 μg cm−2 of silver ions caused a 6 log10 reduction in colony forming units of Staphylococcus epidermidis and Pseudomonas aeruginosa within 12 h. Significantly, this level of silver release is below that which is cytotoxic to NIH 3T3 mouse fibroblast cells. Overall, this study describes a general and facile approach for the functionalization of biomaterial surfaces without subjecting them to potentially deleterious processing conditions.
A peptide-based, injectable hydrogel is designed that is inherently antibacterial and can kill rnethidllin-resistarrf Staphylococcus aureus (MRSA) on contact. Peptide gels can be used as coatings to inhibit MRSA infection or syringe-delivered to a contaminated surface where the gel kills MRSA on contact.
A novel graphene oxide-doxorubicin hydrochloride nanohybrid (GO-DXR) was prepared via a simple noncovalent method, and the loading and release behaviors of DXR on GO were investigated. An efficient loading of DXR on GO as high as 2.35 mg/mg was obtained at the initial DXR concentration of 0.47 mg/mL. The loading and release of DXR on GO showed strong pH dependence, which may be due to the hydrogen-bonding interaction between GO and DXR. The fluorescent spectrum and electrochemical results indicate that strong π-π stacking interaction exists between them.
A detailed description of the electronic properties, chemical state, and structure of uniform single and few-layered graphene oxide (GO) thin films at different stages of reduction is reported. The residual oxygen content and structure of GO are monitored and these chemical and structural characteristics are correlated to electronic properties of the thin films at various stages of reduction. It is found that the electrical characteristics of reduced GO do not approach those of intrinsic graphene obtained by mechanical cleaving because the material remains significantly oxidized. The residual oxygen forms sp3 bonds with carbon atoms in the basal plane such that the carbon sp2 bonding fraction in fully reduced GO is ∼0.80. The minority sp3 bonds disrupt the transport of carriers delocalized in the sp2 network, limiting the mobility, and conductivity of reduced GO thin films. Extrapolation of electrical conductivity data as a function of oxygen content reveals that complete removal of oxygen should lead to properties that are comparable to graphene.
Oxidative stress induced by reactive oxygen species (ROS) is one of the most important antibacterial mechanisms of engineered nanoparticles (NPs). To elucidate the ROS generation mechanisms, we investigated the ROS production kinetics of seven selected metal-oxide NPs and their bulk counterparts under UV irradiation (365 nm). The results show that different metal oxides had distinct photogenerated ROS kinetics. Particularly, TiO(2) nanoparticles and ZnO nanoparticles generated three types of ROS (superoxide radical, hydroxyl radical, and singlet oxygen), whereas other metal oxides generated only one or two types or did not generate any type of ROS. Moreover, NPs yielded more ROS than their bulk counterparts likely due to larger surface areas of NPs providing more absorption sites for UV irradiation. The ROS generation mechanism was elucidated by comparing the electronic structures (i.e., band edge energy levels) of the metal oxides with the redox potentials of various ROS generation, which correctly interpreted the ROS generation of most metal oxides. To develop a quantitative relationship between oxidative stress and antibacterial activity of NPs, we examined the viability of E. coli cells in aqueous suspensions of NPs under UV irradiation, and a linear correlation was found between the average concentration of total ROS and the bacterial survival rates (R(2) = 0.84). Although some NPs (i.e., ZnO and CuO nanoparticles) released toxic ions that partially contributed to their antibacterial activity, this correlation quantitatively linked ROS production capability of NPs to their antibacterial activity as well as shed light on the applications of metal-oxide NPs as potential antibacterial agents.
We describe here new nanoparticles based on the bioconjugation of penicillin G to squalene in order to overcome severe intracellular infections by pathogen bacteria whose mechanism of resistance arises from the poor intracellular diffusion of several antibiotics. Two different squalene-penicillin G conjugates were synthesized (pH-sensitive and pH-insensitive), and their self-assembly as nanoparticles was investigated through morphology and stability studies. These nanoparticles had a size of 140 ± 10 nm (polydispersity index of 0.1) and a negative charge, and they did not display any supramolecular organization. Furthermore, they were found stable in water and in different culture medium. The cellular uptake and localization of these fluorescently labeled nanoparticles were explored on the macrophage cell line J774 by flow cytometry and confocal microscopy analysis. The squalenoylated nanoparticles were found to be cell internalized through clathrin-dependent and -independent endocytic pathways. Moreover, they induced an improved intracellular antibacterial activity on the facultative intracellular pathogen S. aureus, compared with free penicillin G, despite the absence of co-localization between the bacteria and the nanoparticles in the cells. This study suggests that the bioconjugation of an antibiotic to a squalene template could be a valuable approach for overcoming the antibiotic resistance due to intracellular bacterial infections.
A study was conducted to demonstrate that a synthetic catecholamine polymer, influenced by by mussel adhesive protein absorbs to all surfaces and can serve as a platform for layer-by-layer (LbL) assembly in a surface-independent manner. Poly(ethylenimine) (PEI), a cationic polymer, was conjugated with 3-(3,4-dihydroxyphenyl)propionic acid, to make catechol-functionalized PEI (PEI-C). It was observed that the degree of catechol modification in PEI-C is 63%, as determined by the ninhydrin test, preserving the cationic character of the polymer for use in LbL, while mimicking the high catechol content of mussel adhesive proteins at the same time. The study also demonstrated that hyaluronic acid (HA), a linear polysaccharide, was selected for an anionic polymer.
Quaternary ammonium compounds (QACs) are widely distributed in hospitals, industry and cosmetics. Little attention has been focused on the potential impact of QACs on the emergence of antibiotic resistance in patients and the environment. To assess this issue, we conducted a literature review on QAC chemical structure, fields of application, mechanism of action, susceptibility testing, prevalence, and co- or cross-resistance to antibiotics. Special attention was paid to the effects of QACs on microflora; in particular, the issue of the potential of QACs for applying selective pressure on multiple-antibiotic-resistant organisms was raised. It was found that there is a lack of standardised procedures for interpreting susceptibility test results. QACs have different impacts on the minimum inhibitory concentrations of antibacterials depending on the antibacterial compound investigated, the resistance genes involved, the measuring methodology and the interpretative criteria. The unmet needs for adequate detection of reduced susceptibility to QACs and antibiotics include (i) a consensus definition for resistance, (ii) epidemiological cut-off values and (iii) clinical resistance breakpoints. This review advocates the design of international guidelines for QAC use.
A cationic amphiphile, cholest-5en-3β-oxyethyl pyridinium bromide (PY(+) -Chol), is able to efficiently disperse exfoliated graphene (GR) in water by the physical adsorption of PY(+) -Chol on the surface of GR to form stable, dark aqueous suspensions at room temperature. The GR-PY(+) -Chol suspension can then be used to solubilize Tamoxifen Citrate (TmC), a breast cancer drug, in water. The resulting TmC-GR-PY(+) -Chol is stable for a long time without any precipitation. Fluorescence emission and UV absorption spectra indicate the existence of noncovalent interactions between TmC, GR, and PY(+) -Chol in these suspensions. Electron microscopy shows the existence of segregated GR sheets and TmC 'ribbons' in the composite suspensions. Atomic force microscopy indicates the presence of 'extended' structures of GR-PY(+) -Chol, which grows wider in the presence of TmC. The slow time-dependent release of TmC is noticed in a reconstituted cell culture medium, a property useful as a drug carrier. TmC-GR-PY(+) -Chol selectively enhanced the cell death (apoptosis) of the transformed cancer cells compared to normal cells. This potency is found to be true for a wide range of transformed cancer cells viz. HeLa, A549, ras oncogene-transformed NIH3T3, HepG2, MDA-MB231, MCF-7, and HEK293T compared to the normal cell HEK293 in vitro. Confocal microscopy confirmed the high efficiency of TmC-GR-PY(+) -Chol in delivering the drug to the cells, compared to the suspensions devoid of GR.
Health and environmental impacts of graphene-based materials need to be thoroughly evaluated before their potential applications. Graphene has strong cytotoxicity toward bacteria. To better understand its antimicrobial mechanism, we compared the antibacterial activity of four types of graphene-based materials (graphite (Gt), graphite oxide (GtO), graphene oxide (GO), and reduced graphene oxide (rGO)) toward a bacterial model-Escherichia coli. Under similar concentration and incubation conditions, GO dispersion shows the highest antibacterial activity, sequentially followed by rGO, Gt, and GtO. Scanning electron microscope (SEM) and dynamic light scattering analyses show that GO aggregates have the smallest average size among the four types of materials. SEM images display that the direct contacts with graphene nanosheets disrupt cell membrane. No superoxide anion (O(2)(•-)) induced reactive oxygen species (ROS) production is detected. However, the four types of materials can oxidize glutathione, which serves as redox state mediator in bacteria. Conductive rGO and Gt have higher oxidation capacities than insulating GO and GtO. Results suggest that antimicrobial actions are contributed by both membrane and oxidation stress. We propose that a three-step antimicrobial mechanism, previously used for carbon nanotubes, is applicable to graphene-based materials. It includes initial cell deposition on graphene-based materials, membrane stress caused by direct contact with sharp nanosheets, and the ensuing superoxide anion-independent oxidation. We envision that physicochemical properties of graphene-based materials, such as density of functional groups, size, and conductivity, can be precisely tailored to either reducing their health and environmental risks or increasing their application potentials.
It is known that many potent, often aromatic drugs are water insoluble, which has hampered their use for disease treatment. In this work, we functionalized nanographene oxide (NGO), a novel graphitic material, with branched polyethylene glycol (PEG) to obtain a biocompatible NGO-PEG conjugate stable in various biological solutions, and used them for attaching hydrophobic aromatic molecules including a camptothecin (CPT) analogue, SN38, noncovalently via pi-pi stacking. The resulting NGO-PEG-SN38 complex exhibited excellent water solubility while maintaining its high cancer cell killing potency similar to that of the free SN38 molecules in organic solvents. The efficacy of NGO-PEG-SN38 was far higher than that of irinotecan (CPT-11), a FDA-approved water soluble SN38 prodrug used for the treatment of colon cancer. Our results showed that graphene is a novel class of material promising for biological applications including future in vivo cancer treatment with various aromatic, low-solubility drugs.
Silicon nanowires (SiNWs), as a novel one-dimensional semiconducting nanomaterial, are attracting increasing interest in recent years. The synthesis of SiNWs with in situ grown silver nanoparticles (AgNPs) (SiNWs@AgNPs) is reported and the highly effective and long-term antibacterial activity of this novel nanostructure is demonstrated.
Hyperbranched polymers (HBPs) are highly branched macromolecules with a three-dimensional dendritic architecture. Due to their unique topological structure and interesting physical/chemical properties, HBPs have attracted wide attention from both academia and industry. In this paper, the recent developments in HBP self-assembly and their biomedical applications have been comprehensively reviewed. Many delicate supramolecular structures from zero-dimension (0D) to three-dimension (3D), such as micelles, fibers, tubes, vesicles, membranes, large compound vesicles and physical gels, have been prepared through the solution or interfacial self-assembly of amphiphilic HBPs. In addition, these supramolecular structures have shown promising applications in the biomedical areas including drug delivery, protein purification/detection/delivery, gene transfection, antibacterial/antifouling materials and cytomimetic chemistry. Such developments promote the interdiscipline researches among surpramolecular chemistry, biomedical chemistry, nano-technology and functional materials.
Interest in graphene centres on its excellent mechanical, electrical,
thermal and optical properties, its very high specific surface area, and
our ability to influence these properties through chemical
functionalization. There are a number of methods for generating graphene
and chemically modified graphene from graphite and derivatives of
graphite, each with different advantages and disadvantages. Here we
review the use of colloidal suspensions to produce new materials
composed of graphene and chemically modified graphene. This approach is
both versatile and scalable, and is adaptable to a wide variety of
applications.
Isolated graphene, a nanometer-thick two-dimensional analog of fullerenes and carbon nanotubes, has recently sparked great excitement in the scientific community given its excellent mechanical and electronic properties. Particularly attractive is the availability of bulk quantities of graphene as both colloidal dispersions and powders, which enables the facile fabrication of many carbon-based materials. The fact that such large amounts of graphene are most easily produced via the reduction of graphene oxide--oxygenated graphene sheets covered with epoxy, hydroxyl, and carboxyl groups--offers tremendous opportunities for access to functionalized graphene-based materials. Both graphene oxide and graphene can be processed into a wide variety of novel materials with distinctly different morphological features, where the carbonaceous nanosheets can serve as either the sole component, as in papers and thin films, or as fillers in polymer and/or inorganic nanocomposites. This Review summarizes techniques for preparing such advanced materials via stable graphene oxide, highly reduced graphene oxide, and graphene dispersions in aqueous and organic media. The excellent mechanical and electronic properties of the resulting materials are highlighted with a forward outlook on their applications.
Most antibiotic resistance mechanisms are associated with a fitness cost that is typically
observed as a reduced bacterial growth rate. The magnitude of this cost is the main
biological parameter that influences the rate of development of resistance, the stability of
the resistance and the rate at which the resistance might decrease if antibiotic use were
reduced. These findings suggest that the fitness costs of resistance will allow susceptible
bacteria to outcompete resistant bacteria if the selective pressure from antibiotics is
reduced. Unfortunately, the available data suggest that the rate of reversibility will be
slow at the community level. Here, we review the factors that influence the fitness costs of
antibiotic resistance, the ways by which bacteria can reduce these costs and the possibility
of exploiting them.
A simple synthetic route for the preparation of functional nanoscale graphene oxide (NGO), a novel nanocarrier for the loading and targeted delivery of anticancer drugs, is reported. The NGO is functionalized with sulfonic acid groups, which render it stable in physiological solution, followed by covalent binding of folic acid (FA) molecules to the NGO, thus allowing it to specifically target MCF-7 cells, human breast cancer cells with FA receptors. Furthermore, controlled loading of two anticancer drugs, doxorubicin (DOX) and camptothecin (CPT), onto the FA-conjugated NGO (FA-NGO) via pi-pi stacking and hydrophobic interactions is investigated. It is demonstrated that FA-NGO loaded with the two anticancer drugs shows specific targeting to MCF-7 cells, and remarkably high cytotoxicity compared to NGO loaded with either DOX or CPT only. Considering that the combined use of two or more drugs, a widely adopted clinical practice, often displays much better therapeutic efficacy than that of a single drug, the controlled loading and targeted delivery of mixed anticancer drugs using these graphene-based nanocarriers may find widespread application in biomedicine.
Liposomes are currently in common use as universal drug carriers in the cosmetic and pharmaceutical industries. The manipulation of different physicochemical properties of liposomes enables the design of particular carriers with the desired pharmacokinetic and pharmacodynamic properties. Most studies regarding liposomal antibiotics deal with aminoglycosides, quinolones, polypeptides, and betalactames. Some of the studies focused on improving pharmacokinetics and reducing toxicity, while others involved enhancing antibacterial activity. In an era of an avalanche of increasing bacterial resistance and severe problems in treating bacterial infections, the application of liposomal antibiotic carriers could be useful, but the high cost of liposome preparation and treatment should also be considered.