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Extracellular matrix-based targeted delivery of particle-based DDS. (A) Schematic of ELP-CLP conjugate-based thermoresponsive nanovesicles (Luo et al., 2017). Copyright 2017. Reproduced with permission from American chemical society. (B) RGD dendrimer peptide modified polyethyleneimine-grafted chitosan for siRNA delivery. In vivo tumor growth of treatment with non-RGD-modified system (PgWSC) and RGD-modified system (RpgWSC), and non-treatment (Y.M. Kim et al., 2017). Copyright 2017. Reproduced with permission from Elsevier Inc. (C) Confocal images of internalization of dendrimer particles (CMCht/PAMAM and YIGSR-CMCht/PAMAM) on HCT-116 cancer cells (red) and L929 fibroblasts (blue) (Carvalho et al., 2019). Copyright Wiley-VCH Verlag GmbH. & Co. KGaA. Reproduced with permission.
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The use of drug delivery vehicles to improve the efficacy of drugs and to target their action at effective concentrations over desired periods of time has been an active topic of research and clinical investigation for decades. Both synthetic and natural drug delivery materials have facilitated locally controlled as well as targeted drug delivery....
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... However, the advantages of increased resistance to proteolytic breakdown, which may be accomplished by replacing the protein core with an alternative polymer, may outweigh the disadvantages that arise from the loss of protein core functions. Further research is required to obtain a more accurate assessment of the equilibrium between functional imitation and effective therapeutics (Pratta et al., 2003;Pauly et al., 2017;Moorehead et al., 2019;Murphy et al., 2019;Hwang et al., 2020;Lanzi et al., 2020;Rizzo et al., 2022;Yao et al., 2022; Frontiers in Cell and Developmental Biology frontiersin.org ...
Proteoglycans (PGs), which have glycosaminoglycan chains attached to their protein cores, are essential for maintaining the morphology and function of healthy body tissues. Extracellular PGs perform various functions, classified into the following four categories: i) the modulation of tissue mechanical properties; ii) the regulation and protection of the extracellular matrix; iii) protein sequestration; and iv) the regulation of cell signaling. The depletion of PGs may significantly impair tissue function, encompassing compromised mechanical characteristics and unregulated inflammatory responses. Since PGs play critical roles in the function of healthy tissues and their synthesis is complex, the development of PG mimetic molecules that recapitulate PG functions for tissue engineering and therapeutic applications has attracted the interest of researchers for more than 20 years. These approaches have ranged from semisynthetic graft copolymers to recombinant PG domains produced by cells that have undergone genetic modifications. This review discusses some essential extracellular PG functions and approaches to mimicking these functions.
... S. aureus-related bone infection results in the secretion of cytokines and chemokines and the overexpression of specific proteins by bone cells (Josse et al. 2015;Schrum et al. 2003). The specific cell or tissue receptors that are overexpressed in certain diseases could be utilized as targets for the delivery of therapeutics (Emami and Ansarypour 2019;Hwang et al. 2020;Large et al. 2019;Srinivasarao and Low 2017). A schematic representation of the targeting of overexpressed receptors during intracellular osteoblast infection is given in Fig. 4. ...
Bone infections caused by Staphylococcus aureus may lead to an inflammatory condition called osteomyelitis, which results in progressive bone loss. Biofilm formation, intracellular survival, and the ability of S. aureus to evade the immune response result in recurrent and persistent infections that present significant challenges in treating osteomyelitis. Moreover, people with diabetes are prone to osteomyelitis due to their compromised immune system, and in life-threatening cases, this may lead to amputation of the affected limbs. In most cases, bone infections are localized; thus, early detection and targeted therapy may prove fruitful in treating S. aureus-related bone infections and preventing the spread of the infection. Specific S. aureus components or overexpressed tissue biomarkers in bone infections could be targeted to deliver active therapeutics, thereby reducing drug dosage and systemic toxicity. Compounds like peptides and antibodies can specifically bind to S. aureus or overexpressed disease markers and combining these with therapeutics or imaging agents can facilitate targeted delivery to the site of infection. The effectiveness of photodynamic therapy and hyperthermia therapy can be increased by the addition of targeting molecules to these therapies enabling site-specific therapy delivery. Strategies like host-directed therapy focus on modulating the host immune mechanisms or signaling pathways utilized by S. aureus for therapeutic efficacy. Targeted therapeutic strategies in conjunction with standard surgical care could be potential treatment strategies for S. aureus-associated osteomyelitis to overcome antibiotic resistance and disease recurrence. This review paper presents information about the targeting strategies and agents for the therapy and diagnostic imaging of S. aureus bone infections.
... abnormal cells/tissues/organs as image-guided therapies ., 2010; Hoppenz et al., 2020;Yazdi et al., 2020;Majumdar and Siahaan, 2012;Rozovsky et al., 2019; ., 2019; Guo et al., 2020;Cherkasov et al., ., 2019;Ebaston et al., 2019;Chin et al., ., 2016;Hwang et al., 2020;Ozturk-Atar et al., 2018;Pattni and Torchilin, 2015;Patsenker and Gellerman, ., 2019). To investigate drug delivery by drug release in biological systems, molecular imagings through spatial and temporal integrated resolutionsbased positron emission tomography (PET) and computed tomography (CT), and to study dual-signal ratiometric drug delivery, Forster/fluorescence resonance energy transfer based fluorescence and confocal laser scanning microscopies have been employed as main fluorescencebased approaches due to their non-invasiveness, high resolution, real time detection, quantitative/qualitative ability ifferent biological systems such as tissue-based single cells, samples and animal models (Eter, 2009;Li et al., 2020; ., 2016; Mandal, 2023). ...
... Many studies are aimed at overcoming the high rate of biodegradation of collagen-based materials, as well as the inclusion of various biologically active compounds in the collagen matrix (for example, antibacterial agents such as ceftazidime and doxycycline [8][9][10], or compounds that promote tissue regeneration [11][12][13]). The collagen matrix is considered as a carrier for the targeted delivery of biologically active substances, from which compounds are released gradually, so that they are able to have a prolonged effect at the site of injury [14][15][16]. To stabilize the structure of collagen and materials based on it, the polypeptide chains of this biopolymer are crosslinked. ...
... In addition to retaining various active components and growth factors in the ECM, 3D model can also promote cell repair and cell function recovery. Compared with Matrigel, acellular matrix has more advantages in cytocompatibility, biocompatibility, immunogenicity and mechanical properties [126,127]. In addition, the 3D microtumor model also has the following advantages: (1) it can retain the collagen structure in the extracellular matrix, has low immunogenicity, good biocompatibility and mechanical properties, and can promote cell adhesion growth and tissue regeneration; (2) no toxic products, no immunogenicity or low immunogenicity; (3) the complex three-dimensional porous microstructure of tissues is preserved to ensure the effective transportation of nutrients and metabolic wastes during cell culture [128]; and (4) excellent biocompatibility and good biomechanical properties. ...
Infantile hemangioma (IH) is the most prevalent benign vascular tumor in infants, with distinct disease stages and durations. Despite the fact that the majority of IHs can regress spontaneously, a small percentage can cause disfigure-ment or even be fatal. The mechanisms underlying the development of IH have not been fully elucidated. Establishing stable and reliable IH models provides a standardized experimental platform for elucidating its pathogenesis, thereby facilitating the development of new drugs and the identification of effective treatments. Common IH models include the cell suspension implantation model, the viral gene transfer model, the tissue block transplantation model, and the most recent three-dimensional (3D) microtumor model. This article summarizes the research progress and clinical utility of various IH models, as well as the benefits and drawbacks of each. Researchers should select distinct IH models based on their individual research objectives to achieve their anticipated experimental objectives, thereby increasing the clinical relevance of their findings.
... Second, cancer cells can develop unique molecular machinery to escape chemotherapy and immunotherapya phenomenon so-called drug-resistant mechanism of cancer cells. The use of advanced drug delivery systems (DDSs) appears to enhance the effectiveness of drugs through specific targeting of diseased cells [8]. Accordingly, targeted DDSs have been developed to treat OS [9]. ...
Bone tumors are relatively rare, which are complex cancers and mostly involve the long bones and pelvis. Bone cancer is mainly categorized into osteosarcoma (OS), chondrosarcoma, and Ewing sarcoma. Of these, OS is the most intimidating cancer of the bone tissue, which is mostly found in the log bones in young children and older adults. Conspicuously, the current chemotherapy modalities used for the treatment of OS often fail mainly due to (i) the non-specific detrimental effects on normal healthy cells/tissues, (ii) the possible emergence of drug resistance mechanisms by cancer cells, and (iii) difficulty in the efficient delivery of anticancer drugs to the target cells. To impose the maximal therapeutic impacts on cancerous cells, it is of paramount necessity to specifically deliver chemotherapeutic agents to the tumor site and target the diseased cells using advanced nanoscale multifunctional drug delivery systems (DDSs) developed using organic and inorganic nanosystems. In this review, we provide deep insights into the development of various DDSs applied in targeting and eradicating OS. We elaborate on different DDSs developed using biomaterials, including chitosan, collagen, poly(lactic acid), poly(lactic-co-glycolic acid), polycaprolactone, poly(ethylene glycol), polyvinyl alcohol, polyethyleneimine, quantum dots, polypeptide, lipid NPs, and exosomes. We also discuss DDSs established using inorganic nanoscale materials such as magnetic NPs, gold, zinc, titanium NPs, ceramic materials, silica, silver NPs, and platinum NPs. We further highlight anticancer drugs' role in bone cancer therapy and the biocompatibility of nanocarriers for OS treatment.
... This is why iLNPs can be kept for a long time in storage conditions while in hours disintegrates once in the body. Indeed, it has been reported that it is below c.a. 30 nm in diameter (87), where NPs cannot support the high surface energy anymore and tends to dissolve. The driving force behind dissolution strongly depends on the solubility of the constituent ions in a given environment and their concentration gradients in the solution. ...
... The first natural barrier the iLNPs need to cross is the biological fluids, blood or lymph, sweat or tear, and the corresponding extracellular matrix, consisting of macromolecules and minerals that change in different tissues, compartments, and health status (88). To overcome these barriers, some iLNPs can interact with particular matrix components that facilitate the interaction with the target cell and the entrance by endocytosis (87). The second natural barrier is the mononuclear phagocyte system, capable of recognizing foreign substances and commensal organisms when entering the body, labelling them with opsonins and enhancing uptake by phagocytic cells, such as kupffer cells in the liver. ...
The long quest for efficient drug administration has been looking for a universal carrier that can precisely transport traditional drugs, new genomic and proteic therapeutic agents. Today, researchers have found conditions to overcome the two main drug delivery dilemmas. On the one side, the versatility of the vehicle to efficiently load, protect and transport the drug and then release it at the target place. On the other hand, the questions related to the degree of PEGylation which are needed to avoid nanoparticle (NP) aggregation and opsonization while preventing cellular uptake. The development of different kinds of lipidic drug delivery vehicles and particles has resulted in the development of ionizable lipid nanoparticles (iLNPs), which can overcome most of the typical drug delivery problems. Proof of their success is the late approval and massive administration as the prophylactic vaccine for SARS-CoV-2. These ILNPs are built by electrostatic aggregation of surfactants, the therapeutic agent, and lipids that self-segregate from an aqueous solution, forming nanoparticles stabilized with lipid polymers, such as PEG. These vehicles overcome previous limitations such as low loading and high toxicity, likely thanks to low charge at the working pH and reduced size, and their entry into the cells via endocytosis rather than membrane perforation or fusion, always associated with higher toxicity. We herein revise their primary features, synthetic methods to prepare and characterize them, pharmacokinetic (administration, distribution, metabolization and excretion) aspects, and biodistribution and fate. Owing to their advantages, iLNPs are potential drug delivery systems to improve the management of various diseases and widely available for clinical use.
... Collagen synthesis increases in severe liver fibrosis (F3 and F4) compared with a healthy liver (fibrillar collagen types I, III and V) [84,85]. In fact, collagen and other ECM proteins are used as biomarkers to determine the stage of fibrosis and as predictors of cancer development [73,86,87]. It is possible that the use of CMS containing similar collagen to healthy livers from human or other mammal sources (such as ® Nukbone) improves the regeneration process. ...
Approximately 1.5 billion chronic liver disease (CLD) cases have been estimated worldwide, encompassing a wide range of liver damage severities. Moreover, liver disease causes approximately 1.75 million deaths per year. CLD is typically characterized by the silent and progressive deterioration of liver parenchyma due to an incessant inflammatory process, cell death, over deposition of extracellular matrix proteins, and dysregulated regeneration. Overall, these processes impair the correct function of this vital organ. Cirrhosis and liver cancer are the main complications of CLD, which accounts for 3.5% of all deaths worldwide. Liver transplantation is the optimal therapeutic option for advanced liver damage. The liver is one of the most common organs transplanted; however, only 10% of liver transplants are successful. In this context, regenerative medicine has made significant progress in the design of biomaterials, such as collagen matrix scaffolds, to address the limitations of organ transplantation (e.g., low donation rates and biocompatibility). Thus, it remains crucial to continue with experimental and clinical studies to validate the use of collagen matrix scaffolds in liver disease.
... 155 The binding between targeting molecules and receptors takes place via endosome-depending mechanism, in which cancer cells can be directly killed. 156 Table 4 demonstrates both active targeting (targeting molecule and its targeted receptor), the effect of passive targeting (EPR effect) which can be seen from the physicochemical characteristics of the prepared nanoparticles, and their impact on the colon cancer cell lines. ...
As per the WHO, colorectal cancer (CRC) caused around 935,173 deaths worldwide in 2020 in both sexes and at all ages.
The available anticancer therapies including chemotherapy, radiotherapy and anticancer drugs are all associated with limited
therapeutic efficacy, adverse effects and low chances. This has urged to emerge several novel therapeutic agents as potential therapies
for CRC including synthetic and natural materials. Orally administrable and targeted drug delivery systems are attractive strategies for
CRC therapy as they minimize the side effects, enhance the efficacy of anticancer drugs. Nevertheless, oral drug delivery till today
faces several challenges like poor drug solubility, stability, and permeability. Various oral nano-based approaches and targeted drug
delivery systems have been developed recently, as a result of the ability of nanoparticles to control the release of the encapsulant, drug
targeting and reduce the number of dosages administered. The unique physicochemical properties of chitosan polymer assist to
overcome oral drug delivery barriers and target the colon tumour cells. Chitosan-based nanocarriers offered additional improvements
by enhancing the stability, targeting and bioavailability of several anti-colorectal cancer agents. Modified chitosan derivatives also
facilitated CRC targeting through strengthening the protection of encapsulant against acidic and enzyme degradation of gastrointestinal
track (GIT). This review aims to provide an overview of CRC pathology, therapy and the barriers against oral drug delivery. It also
emphasizes the role of nanotechnology in oral drug targeted delivery system and the growing interest towards chitosan and its
derivatives. The present review summarizes the relevant works to date that have studied the potential applications of chitosan-based
nanocarrier towards CRC treatment
Keywords: chitosan, colorectal cancer, nanocarriers, oral delivery, drug targeting, nanotechnology
... In KEGG enrichment analysis, the enrichment results of the shared DEGs between MS vs. C and HS vs. C groups showed that the heat stresses influenced "ECM-receptor interaction" pathway ( Figure 1B). "ECM-receptor interaction" pathway is closely related to the maintenance of organismal health (Hwang et al., 2020;Sainio and Järveläinen, 2020). Thus, the enrichment in "ECM-receptor interaction" pathway suggests that heat stress may damage the balance of skin health via ECMreceptor interaction pathway. ...
Heat stress induced by global warming has damaged the well-being of aquatic animals. The skin tissue plays a crucial role as a defense barrier to protect organism, however, little is known about the effect of heat stress on fish skin, particularly in cold-water fish species. Here, we investigated the effects of mild heat stress (24°C, MS) and high heat stress (28°C, HS) on Siberian sturgeon skin using RNA-seq, histological observation, and microbial diversity analysis. In RNA-seq, 8,819 differentially expressed genes (DEGs) in MS vs. C group and 12,814 DEGs in HS vs. C group were acquired, of which the MS vs. C and HS vs. C groups shared 3,903 DEGs, but only 1,652 DEGs were successfully annotated. The shared DEGs were significantly enriched in pathways associating with mucins synthesis. Histological observation showed that the heat stresses significantly reduced the number of skin mucous cells and induced the damages of epidermis. The microbial diversity analysis elicited that heat stress markedly disrupted the diversity and abundance of skin microbiota by increasing of potential pathogens (Vibrionimonas, Mesorhizobium, and Phyllobacterium) and decreasing of probiotics (Bradyrhizobium and Methylovirgula). In conclusion, this study reveals that heat stress causes adverse effects on sturgeon skin, reflecting in decreasing the mucus secretion and disordering the mucosal microbiota, which may contribute to develop the preventive strategy for heat stress caused by global warming.
