International Journal of Nanomedicine

Publisher: Dove Medical Press


An international, peer-reviewed journal focusing on the application of nanotechnology in diagnostics, therapeutics, and drug delivery systems throughout the biomedical field. Reflecting the growing activity in this emerging specialty, the aim of this journal is to highlight research and development leading to potential clinical applications in the prevention and treatment of disease.

Impact factor 4.20

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  • Website
    International Journal of Nanomedicine website
  • Other titles
    Int. j. nanomedicine
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  • Material type
    Periodical, Internet resource
  • Document type
    Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details

Dove Medical Press

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    • On institutional repository, central repository or subject -based repository, including PubMed Central
    • Creative Commons Attribution Non-Commercial License
    • UK funded authors may use a Creative Commons Attribution License
    • On a non-profit server
    • Must link to publisher version
    • Published source (journal and Dove Medical Press) must be acknowledged as original place of publication
    • Publisher's version/PDF may be used
    • All titles are open access journals
    • Publisher last contacted on 20/01/2013
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Publications in this journal

  • Eloisa Berbel Manaia, Renata Cristina Kiatkoski Kaminski, A nselmo Gomes de Oliveira, Marcos Antonio Corrêa, Leila Aparecida Chiavacci
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    ABSTRACT: Multifunctional products have been developed to combine the benefits of functional components and terpinen-4-ol (TP) delivery systems. In this way, p-toluene sulfonic acid modified titanium dioxide (TiO2) nanoparticles and TP, an antioxidant, have been incorporated in liquid-crystalline formulations for photoprotection and controlled release of the TP, respectively. By X-ray powder diffraction and diffuse reflectance spectroscopy, we noted that using p-toluene sulfonic acid as a surface modifier made it possible to obtain smaller and more transparent TiO2 nanoparticles than those commercially available. The liquid-crystalline formulation containing the inorganic ultraviolet filter was classified as broad-spectrum performance by the absorbance spectroscopy measurements. The formulations containing modified TiO2 nanoparticles and TP were determined to be in the hexagonal phase by polarized light microscopy and small-angle X-ray scattering, which makes possible the controlled released of TP following zero-order kinetics. The developed formulations can control the release of TP. Constant concentrations of the substance have been released per time unit, and the modified TiO2 nanoparticles can act as a transparent inorganic sunscreen.
    International Journal of Nanomedicine 01/2015; 10:811.
  • Braicu C, Cojocneanu-Petric R, Chira S, Truta A, Floares A, Petrut B, Achimas-Cadariu P, Berindan-Neagoe I
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    ABSTRACT: MicroRNAs (miRNAs) are small, noncoding RNA species with a length of 20–22 nucleotides that are recognized as essential regulators of relevant molecular mechanisms, including carcinogenesis. Current investigations show that miRNAs are detectable not only in different tissue types but also in a wide range of biological fluids, either free or trapped in circulating microvesicles. miRNAs were proven to be involved in cell communication, both in pathological and physiological processes. Evaluation of the global expression patterns of miRNAs provides key opportunities with important practical applications, taking into account that they modulate essential biological processes such as epithelial to mesenchymal transition, which is a mechanism relevant in bladder cancer. miRNAs collected from biological specimens can furnish valuable evidence with regard to bladder cancer oncogenesis, as they also have been linked to clinical outcomes in urothelial carcinoma. Therefore, a single miRNA or a signature of multiple miRNAs may improve risk stratification of patients and may supplement the histological diagnosis of urological tumors, particularly for bladder cancer.
    International Journal of Nanomedicine 01/2015; 2015(10):791-800.
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    ABSTRACT: Despite suffering from the major disadvantage of low sensitivity, microscopy of direct smear with the Ziehl-Neelsen stain is still broadly used for detection of acid-fast bacilli and diagnosis of tuberculosis. Here, we present a unique detection method of Mycobacterium tuberculosis (MTB) using surface functionalized magnetic microspheres (MMSs) coupled with quantum dots (QDs), conjugated with various antibodies and phage display-derived peptides. The principle is based upon the conformation of the sandwich complex composed of bacterial cells, MMSs, and QDs. The complex system is tagged with QDs for providing the fluorescent signal as part of the detection while magnetic separation is achieved by MMSs. The peptide ligand H8 derived from the phage display library Ph.D.-7 is developed for MTB cells. Using the combinations of MMS-polyclonal antibody+QD-H8 and MMS-H8+QD-H8, a strong signal of 10(3) colony forming units (CFU)/mL H37Rv was obtained with improved specificity. MS-H8+QD-H8 combination was further optimized by adjusting the concentrations of MMSs, QDs, and incubation time for the maximum detection signal. The limit of detection for MTB was found to reach 10(3) CFU/mL even for the sputum matrices. Positive sputum samples could be distinguished from control. Thus, this novel method is shown to improve the detection limit and specificity of MTB from the sputum samples, and to reduce the testing time for accurate diagnosis of tuberculosis, which needs further confirmation of more clinical samples.
    International Journal of Nanomedicine 01/2015; 10:77-88.
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    ChunXia Yao, XiaoLi Shi, Xiao Lin, Lan Shen, DeSheng Xu, Yi Feng
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    ABSTRACT: Although PEGylation plays an important role in drug delivery, knowledge about the distribution behavior of PEGylated drugs in ischemic myocardia is rather limited compared to nanoparticles. This work therefore aims to characterize the targeting behavior of the anti-myocardial ischemic mono-PEGylated conjugates of Radix Ophiopogonis polysaccharide (ROP) in two clinically relevant animal models, ie, the myocardial infarction (MI) model and the ischemia/reperfusion (IR) model. To determine the effect of the molecular size of conjugates, two representative conjugates (20- and 40-kDa polyethylene glycol mono-modified ROPs), with hydrodynamic size being approximately and somewhat beyond 10 nm, respectively, were studied in parallel at three time points postdose after a method for determining them quantitatively in biosamples was established. The results showed that the cardiac distribution of the two conjugates was significantly enhanced in both MI and IR rats due to the enhanced permeability and retention effect induced by ischemia. In general, the cardiac targeting efficacy of the conjugates in MI and IR rats was approximately 2; however, different changing in targeting efficacy with time was observed between MI and IR rats and also between the conjugates. Although the enhanced permeability and retention effect-based targeting efficacy for mono-PEGylated ROPs was not high, they, as dissolved macromolecules, are prone to diffusion in the cardiac interstitium space, and thus, facilitate the drug to reach perfusion-deficient and nonperfused areas. These findings are helpful in choosing the cardiac targeting strategy.
    International Journal of Nanomedicine 01/2015; 10:409-18.
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    ABSTRACT: Cationic charged chitosan as stabilizer was evaluated in preparation of nanocrystals using probe sonication method. The influence of cationic charge densities of chitosan (low CSL, medium CSM, high CSH molecular weights) and Labrasol(®) in solubility enhancement and modifying the release was investigated, using atorvastatin (ATR) as poorly soluble model drug. Compared to CSM and CSH; low cationic charge of CSL acted as both electrostatic and steric stabilizer by significant size reduction to 394 nm with charge of 21.5 meV. Solubility of ATR-CSL increased to 60-fold relative to pure ATR and ATR-L. Nanocrystals were characterized for physiochemical properties. Scanning electron microscopy revealed scaffold-like structures with high surface area. X-ray powder diffractometry and differential scanning calorimetry revealed crystalline to slight amorphous state changes after cationic charge size reduction. Fourier transform-infrared spectra indicated no potent drug-excipient interactions. The enhanced dissolution profile of ATR-CSL indicates that sustained release was achieved compared with ATR-L and Lipitor(®). Anti-hyperlipidemic performance was pH dependent where ATR-CSL exhibited 2.5-fold higher efficacy at pH 5 compared to pH 6 and Lipitor(®). Stability studies indicated marked changes in size and charge for ATR-L compared to ATR-CSL exemplifying importance of the stabilizer. Therefore, nanocrystals developed with CSL as a stabilizer is a promising choice to enhance dissolution, stability, and in-vivo efficacy of major Biopharmaceutical Classification System II/IV drugs.
    International Journal of Nanomedicine 01/2015; 10:321-34.
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    ABSTRACT: Nanoparticles (NPs) which target specific agents could effectively recognize the target cells and increase the stability of chemical agents by encapsulation. As such, NPs have been widely used in cancer treatment research. Recently, over 90% of treatment failure cases in patients with metastatic cancer were attributed to resistance to chemotherapy. Surface-exposed glucose-regulated protein of 78 kDa (GRP78) is expressed highly on many tumor cell surfaces in many human cancers and is related to the regulation of invasion and metastasis. Herein, we report that NPs conjugated with antibody against GRP78 (mAb GRP78-NPs) inhibit the adhesion, invasion, and metastasis of hepatocellular carcinoma (HCC) and promote drug delivery of 5-fluorouracil into GRP78 high-expressed human hepatocellular carcinoma cells. Our new findings suggest that mAb GRP78-NPs could enhance drug accumulation by effectively transporting NPs into cell surface GRP78-overexpressed human hepatocellular carcinoma cells and then inhibit cell proliferation and viability and induce cell apoptosis by regulating caspase-3. In brief, mAb GRP78-NPs effectively inhibit cancer cell invasion and enhance antitumor efficiency by targeted drug delivery.
    International Journal of Nanomedicine 01/2015; 10:245-56.
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    Shangyuan Feng, Shaohua Huang, Duo Lin, Guannan Chen, Yuanji Xu, Yongzeng Li, Zufang Huang, Jianji Pan, Rong Chen, Haishan Zeng
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    ABSTRACT: The capability of saliva protein analysis, based on membrane protein purification and surface-enhanced Raman spectroscopy (SERS), for detecting benign and malignant breast tumors is presented in this paper. A total of 97 SERS spectra from purified saliva proteins were acquired from samples obtained from three groups: 33 healthy subjects; 33 patients with benign breast tumors; and 31 patients with malignant breast tumors. Subtle but discernible changes in the mean SERS spectra of the three groups were observed. Tentative assignments of the saliva protein SERS spectra demonstrated that benign and malignant breast tumors led to several specific biomolecular changes of the saliva proteins. Multiclass partial least squares-discriminant analysis was utilized to analyze and classify the saliva protein SERS spectra from healthy subjects, benign breast tumor patients, and malignant breast tumor patients, yielding diagnostic sensitivities of 75.75%, 72.73%, and 74.19%, as well as specificities of 93.75%, 81.25%, and 86.36%, respectively. The results from this exploratory work demonstrate that saliva protein SERS analysis combined with partial least squares-discriminant analysis diagnostic algorithms has great potential for the noninvasive and label-free detection of breast cancer.
    International Journal of Nanomedicine 01/2015; 10:537-47.
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    ABSTRACT: Successful in vivo gene delivery mediated by nonviral vectors requires efficient extracellular and intracellular gene delivery, but few studies have given attention to the former. That is why numerous gene delivery systems have succeeded in vitro, while the expected clinical success has not come about. To realize efficient extracellular gene delivery, the stability of vectors and/or their complexes with genes in body fluids is first required, which prevents loaded genes from premature unloading and degradation. Furthermore, the storage stability of vectors under common conditions is important for their widespread applications. Lipopolysaccharide-amine nanopolymersomes (NPs), a gene vector developed by our group recently, have higher than 95% in vitro transfection efficiency in mesenchymal stem cells when delivering pEGFP, and induce significant angiogenesis in zebrafish when delivering plasmid encoding vascular endothelial growth factor deoxyribonucleic acid (pVEGF). To reveal their extracellular delivery ability and storage stability, in this study their stability in various simulant physiological environments and storage conditions was systematically studied by monitoring their changes in disassembly, size, zeta potential, and transfection efficiency. Additionally, damage to the mitochondria of mesenchymal stem cells was evaluated. Results show that NPs and plasmid deoxyribonucleic acid (pDNA)-loaded NPs (pNPs) have acceptable stability against dilution, anions, salts, pH, enzyme, and serum, presumably assuring their efficient extracellular delivery in vivo. Moreover, both the lyophilized NPs at room temperature and NP/pNP solution at 4°C have high storage stability, and pNPs show low damage to the mitochondria. The acceptable stability of NPs combined with compatibility and efficient gene transfection highlight their huge potential in the clinic as a gene delivery vector.
    International Journal of Nanomedicine 01/2015; 10:597-608.
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    ABSTRACT: The Nanomedicine program at Northeastern University provides a unique interdisciplinary graduate education that combines experiential research, didactic learning, networking, and outreach. Students are taught how to apply nanoscience and nanotechnology to problems in medicine, translate basic research to the development of marketable products, negotiate ethical and social issues related to nanomedicine, and develop a strong sense of community involvement within a global perspective. Since 2006, the program has recruited 50 doctoral students from ten traditional science, technology, and engineering disciplines to participate in the 2-year specialization program. Each trainee received mentoring from two or more individuals, including faculty members outside the student's home department and faculty members at other academic institutions, and/or clinicians. Both students and faculty members reported a significant increase in interdisciplinary scholarly activities, including publications, presentations, and funded research proposals, as a direct result of the program. Nearly 90% of students graduating with a specialization in nanomedicine have continued on to careers in the health care sector. Currently, 43% of graduates are performing research or developing products that directly involve nanomedicine. This article identifies some key elements of the Nanomedicine program, describes how they were implemented, and reports on the metrics of success.
    International Journal of Nanomedicine 01/2015; 10:23-30.
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    ABSTRACT: We describe here a simple synthetic strategy for the fabrication of carbon-coated Fe3O4 (Fe3O4@C) particles using a single-component precursor, iron (III) diethylenetriaminepentaacetic acid complex. Physicochemical analyses revealed that the core of the synthesized particles consists of ferromagnetic Fe3O4 material ranging several hundred nanometers, embedded in nitrogen-doped graphitic carbon with a thickness of ~120 nm. Because of their photothermal activity (absorption of near-infrared [NIR] light), the Fe3O4@C particles have been investigated for photothermal therapeutic applications. An example of one such application would be the use of Fe3O4@C particles in human adenocarcinoma A549 cells by means of NIR-triggered cell death. In this system, the Fe3O4@C can rapidly generate heat, causing >98% cell death within 10 minutes under 808 nm NIR laser irradiation (2.3 W cm(-2)). These Fe3O4@C particles provided a superior photothermal therapeutic effect by intratumoral delivery and NIR irradiation of tumor xenografts. These results demonstrate that one-pot synthesis of carbon-coated magnetic particles could provide promising materials for future clinical applications and encourage further investigation of this simple method.
    International Journal of Nanomedicine 01/2015; 10:271-82.
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    ABSTRACT: Previous studies have indicated that the nephrotoxicity induced by mesoporous silica nanoparticles (MSNs) is closely related to inflammation. Nuclear factor kappa B (NF-κB), a common rapid transcription factor associated with inflammation, plays an important role in the process of many kidney diseases. Acute toxicity assessment with a high-dose exposure is critical for the development of nanoparticle, as a part of standardized procedures for the evaluation of their toxicity. The present study was undertaken to observe the acute toxicity, predict the potential target organs of MSNs injury, and test the hypothesis that the NF-κB pathway plays a role in mediating the acute kidney injury and renal interstitial fibrosis in mice induced by MSNs. Balb/c mice were intraperitoneally injected with MSNs at concentrations of 150, 300, or 600 mg/kg. All of the animals were euthanized 2 and 12 days after exposure, and the blood and kidney tissues were collected for further studies. In vitro, the cytotoxicity, fibrosis markers, and NF-κB pathway were measured in a normal rat kidney cell line (NRK-52E). Acute kidney injury was induced by MSNs in mice after 2 days, some renal tubules regenerated and renal interstitial fibrosis was also observed. The expression of fibrosis markers and the nuclear translocation of NF-κB p65 in the kidney homogenates increased after exposure to MSNs. The in vitro study showed that MSNs cause cytotoxicity in NRK-52E cells and increased the expression of fibrosis markers. In addition, the NF-κB pathway could be induced, and inhibition of the NF-κB pathway could alleviate the fibrosis caused by MSNs. We conclude that inflammation is a major effector of the acute kidney toxicity induced by MSNs and results in renal interstitial fibrosis, which is mediated by the NF-κB signaling pathway.
    International Journal of Nanomedicine 01/2015; 10:1-22.
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    ABSTRACT: Oxidative stress can damage proteins, DNA, and lipids, and is involved in the progression of many diseases. Damage to infected cells caused by oxidative stress is related to increased levels of reactive oxygen species, including hydrogen peroxide. During oxidative stress, hydrogen peroxide levels are often increased and catalase level decreased inside cells. This can lead to the death of skin and other cells. Hydrophobic low molecular weight compounds are useful in treating hemorrhagic conditions of the skin. To this end, cystamine has been successfully conjugated with graphene oxide (GO) as a drug carrier. The current study used the microdilution method to determine the minimum inhibitory concentrations of cystamine-conjugated GO against four types of pathogenic bacteria. Minimum inhibitory concentrations values were 1 μg/mL against Escherichia coli and Salmonella typhimurium, 6 μg/mL against Enterococcus faecalis, and 4 μg/mL against Bacillus subtilis. Toxicity of the conjugate against squamous cell carcinoma 7 cells was minimal at low concentrations, but increased in a dose-dependent manner. These results demonstrated that our protocol produced a cystamine-conjugated GO with low cytotoxicity, but strong reactive oxygen species effects and high antibacterial activity. This nanohybrid may be useful in the treatment of dermatological disorders. Moreover, this class of nanohybrid may have other biomedical applications due to their low cytotoxicity and high antibacterial activity.
    International Journal of Nanomedicine 01/2015; 10:549-56.
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    ABSTRACT: In order to begin to prepare a novel orthopedic implant that mimics the natural bone environment, the objective of this in vitro study was to synthesize nanocrystalline hydroxyapatite (NHA) and coat it on titanium (Ti) using molecular plasma deposition (MPD). NHA was synthesized through a wet chemical process followed by a hydrothermal treatment. NHA and micron sized hydroxyapatite (MHA) were prepared by processing NHA coatings at 500°C and 900°C, respectively. The coatings were characterized before and after sintering using scanning electron microscopy, atomic force microscopy, and X-ray diffraction. The results revealed that the post-MPD heat treatment of up to 500°C effectively restored the structural and topographical integrity of NHA. In order to determine the in vitro biological responses of the MPD-coated surfaces, the attachment and spreading of osteoblasts (bone-forming cells) on the uncoated, NHA-coated, and MHA-coated anodized Ti were investigated. Most importantly, the NHA-coated substrates supported a larger number of adherent cells than the MHA-coated and uncoated substrates. The morphology of these cells was assessed by scanning electron microscopy and the observed shapes were different for each substrate type. The present results are the first reports using MPD in the framework of hydroxyapatite coatings on Ti to enhance osteoblast responses and encourage further studies on MPD-based hydroxyapatite coatings on Ti for improved orthopedic applications.
    International Journal of Nanomedicine 01/2015; 10:527-35.
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    ABSTRACT: This report compares the effect of lipid and polymeric nanoparticles upon human neutrophils in the presence of cationic surfactants. Nanostructured lipid carriers and poly(lactic-co-glycolic) acid nanoparticles were manufactured as lipid and polymeric systems, respectively. Some cytotoxic and proinflammatory mediators such as lactate dehydrogenase (LDH), elastase, O2 (•-), and intracellular Ca(2+) were examined. The nanoparticles showed a size of 170-225 nm. Incorporation of cetyltrimethylammonium bromide or soyaethyl morpholinium ethosulfate, the cationic surfactant, converted zeta potential from a negative to a positive charge. Nanoparticles without cationic surfactants revealed a negligible change on immune and inflammatory responses. Cationic surfactants in both nanoparticulate and free forms induced cell death and the release of mediators. Lipid nanoparticles generally demonstrated a greater response compared to polymeric nanoparticles. The neutrophil morphology observed by electron microscopy confirmed this trend. Cetyltrimethylammonium bromide as the coating material showed more significant activation of neutrophils than soyaethyl morpholinium ethosulfate. Confocal microscope imaging displayed a limited internalization of nanoparticles into neutrophils. It is proposed that cationic nanoparticles interact with the cell membrane, triggering membrane disruption and the following Ca(2+) influx. The elevation of intracellular Ca(2+) induces degranulation and oxidative stress. The consequence of these effects is cytotoxicity and cell death. Caution should be taken when selecting feasible nanoparticulate formulations and cationic additives for consideration of applicability and toxicity.
    International Journal of Nanomedicine 01/2015; 10:371-85.
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    ABSTRACT: CoFe nanowires have been synthesized by the electrodeposition technique into the pores of a polycarbonate membrane with a nominal pore diameter of 50 nm, and the composition of CoFe nanowires varying by changing the source concentration of iron. The synthesized nanowire surfaces were functionalized with amine groups by treatment with aminopropyltriethoxysilane (APTES) linker, and then conjugated with streptavidin-Cy3 protein via ethyl (dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide coupling chemistry. The oxide surface of CoFe nanowire is easily modified with aminopropyltriethoxysilane to form an amine terminating group, which is covalently bonded to streptavidin-Cy3 protein. The physicochemical properties of the nanowires were analyzed through different characterization techniques such as scanning electron microscope, energy dispersive spectroscopy, and vibrating sample magnetometer. Fluorescence microscopic studies and Fourier transform infrared studies confirmed the immobilization of protein on the nanowire surface. In addition, the transmission electron microscope analysis reveals the thin protein layer which is around 12-15 nm on the nanowire surfaces.
    International Journal of Nanomedicine 01/2015; 10:645-51.