Vimentin Targeted Nano-gene Carrier for Treatment of Renal Diseases

Background@#Chronic kidney disease (CKD) is a global health problem, and there is no permanent treatment for reversing kidney failure; thus, early diagnosis and effective treatment are required. Gene therapy has outstanding potential; however, the lack of safe gene delivery vectors, a reasonable transfection rate, and kidney targeting ability limit its application. Nanoparticles can offer innovative ways to diagnose and treat kidney diseases as they facilitate targetability and therapeutic efficacy. @*Methods@#Herein, we developed a proximal renal tubule-targeting gene delivery system based on alternative copolymer (PS) of sorbitol and polyethyleneimine (PEI), modified with vimentin-specific chitobionic acid (CA), producing PS-conjugated CA (PSC) for targeting toward vimentin-expressing cells in the kidneys. In vitro studies were used to determine cell viability, transfection efficiency, serum influence, and specific uptake in the human proximal renal tubular epithelial cell line (HK-2). Finally, the targeting efficiency of the prepared PSC gene carriers was checked in a murine model of Alport syndrome. @*Results@#Our results suggested that the prepared polyplex showed low cytotoxicity, enhanced transfection efficiency, specific uptake toward HK-2 cells, and excellent targeting efficiency toward the kidneys. @*Conclusion@#Collectively, from these results it can be inferred that the PSC can be further evaluated as a potential gene carrier for the kidney-targeted delivery of therapeutic genes for treating diseases.

Multimodal Composite Iron Oxide Nanoparticles for Biomedical Applications

BACKGROUND: Iron oxide nanoparticles (IONPs) are excellent candidates for biomedical imaging because of unique characteristics like enhanced colloidal stability and excellent in vivo biocompatibility. Over the last decade, material scientists have developed IONPs with better imaging and enhanced optical absorbance properties by tuning their sizes, shape, phases, and surface characterizations. Since IONPs could be detected with magnetic resonance imaging, various attempts have been made to combine other imaging modalities, thereby creating a high-resolution imaging platform. Composite IONPs (CIONPs) comprising IONP cores with polymeric or inorganic coatings have recently been documented as a promising modality for therapeutic applications. METHODS: In this review, we provide an overview of the recent advances in CIONPs for multimodal imaging and focus on the therapeutic applications of CIONPs. RESULTS: CIONPs with phototherapeutics, IONP-based nanoparticles are used for theranostic application via imaging guided photothermal therapy. CONCLUSION: CIONP-based nanoparticles are known for theranostic application, longstanding effects of composite NPs in in vivo systems should also be studied. Once such issues are fixed, multifunctional CIONP-based applications can be extended for theranostics of diverse medical diseases in the future.

Injectable Biomaterials in Plastic and Reconstructive Surgery: A Review of the Current Status

BACKGROUND: Injectable biomaterials have attracted increasing attention for volume restoration and tissue regeneration. The main aim of this review is to discuss the current status of the injectable biomaterials for correction of tissue defects in plastic and reconstructive surgery. METHODS: Requirements of injectable biomaterials, mechanism of in situ gelation, characteristics, and the combinational usage of adipose-derived stem cells (ADSCs) and growth factors were reviewed. RESULTS: The ideal injectable biomaterials should be biocompatible, non-toxic, easy to use, and cost-effective. Additionally, it should possess adequate mechanical properties and stability. In situ gelation method includes physical, chemical, enzymatic and photo-initiated methods. Natural and synthetic biomaterials carry their pros and cons due to their inherent properties. The combined use of ADSCs and growth factors provides enhanced potential for adipose tissue regeneration. CONCLUSION: The usage of injectable biomaterials has been increasing for the tissue restoration and regeneration. The future of incorporating ADSCs and growth factors into the injectable biomaterials is promising.

Biopolymeric In Situ Hydrogels for Tissue Engineering and Bioimaging Applications

BACKGROUND: Biopolymeric in situ hydrogels play a crucial role in the regenerative repair and replacement of infected or injured tissue. They possess excellent biodegradability and biocompatibility in the biological system, however only a few biopolymeric in situ hydrogels have been approved clinically. Researchers have been investigating new advancements and designs to restore tissue functions and structure, and these studies involve a composite of biometrics, cells and a combination of factors that can repair or regenerate damaged tissue. METHODS: Injectable hydrogels, cross-linking mechanisms, bioactive materials for injectable hydrogels, clinically applied injectable biopolymeric hydrogels and the bioimaging applications of hydrogels were reviewed. RESULTS: This article reviews the different types of biopolymeric injectable hydrogels, their gelation mechanisms, tissue engineering, clinical applications and their various in situ imaging techniques. CONCLUSION: The applications of bioactive injectable hydrogels and their bioimaging are a promising area in tissue engineering and regenerative medicine. There is a high demand for injectable hydrogels for in situ imaging.

Novel Fabrication of MicroRNA Nanoparticle-Coated Coronary Stent for Prevention of Post-Angioplasty Restenosis

BACKGROUND AND OBJECTIVES: MicroRNA 145 is known to be responsible for cellular proliferation, and its enhanced expression reportedly inhibits the retardation of vascular smooth muscle cell growth specifically. In this study, we developed a microRNA 145 nanoparticle immobilized, hyaluronic acid (HA)-coated stent. MATERIALS AND METHODS: For the gene therapy, we used disulfide cross-linked low molecular polyethylenimine as the carrier. The microRNA 145 was labeled with YOYO-1 and the fluorescent microscopy images were obtained. The release of microRNA 145 from the stent was measured with an ultra violet spectrophotometer. The downstream targeting of the c-Myc protein and green fluorescent protein was determined by Western blotting. Finally, we deployed microRNA 145/ssPEI nanoparticles immobilized on HA-coated stents in the balloon-injured external iliac artery in a rabbit restenosis model. RESULTS: Cellular viability of the nanoparticle-immobilized surface tested using A10 vascular smooth muscle cells showed that MSN exhibited negligible cytotoxicity. In addition, microRNA 145 and downstream signaling proteins were identified by western blots with smooth muscle cell (SMC) lysates from the transfected A10 cell, as the molecular mechanism for decreased SMC proliferation that results in the inhibition of in-stent restenosis. MicroRNA 145 released from the stent suppressed the growth of the smooth muscle at the peri-stent implantation area, resulting in the prevention of restenosis at the post-implantation. We investigated the qualitative analyses of in-stent restenosis in the rabbit model using micro-computed tomography imaging and histological staining. CONCLUSION: MicroRNA 145-eluting stent mitigated in-stent restenosis efficiently with no side effects and can be considered a successful substitute to the current drug-eluting stent.