Stem Cells: Therapeutic Implications in Chemotherapy and Radiotherapy Resistance in Cancer Therapy.

Cancer stem cells (CSCs) are transformed forms of normal stem cells within heterogeneous mixture of cancer cells. These are mainly responsible for the recurrence of cancer after treatment because of their ability to develop resistance against chemo and radiotherapy due to various factors such as activation of signalling pathways important for self-renewal, DNA repair capacity, microenvironment and expression of ABC transporters. Targeting these mechanisms as potential factors can eliminate CSCs, which eventually decreases cancer recurrence. This review focuses on the characteristics of CSCs, their role in the development of resistance to chemotherapy and radiotherapy along with the therapeutic potential targets for successful elimination of CSC population.

Fluorescent Carbon Quantum Dots Functionalized by Poly L-Lysine: Efficient Material for Antibacterial, Bioimaging and Antiangiogenesis Applications.

This study illustrates the synthesis of functionalized carbon quantum dots (CQDs) by the one-pot pyrolysis method. The functionalization agent used in CQD synthesis was poly l- lysine (PLL). Various physicochemical techniques were employed to confirm the successful formation of PLLCQD including High resolution transmission electron microscopy (HR-TEM), UV-Vis spectroscopy, fluorescence spectroscopy; Atomic force microscopy (AFM), X-ray Photoelectron Spectroscopy (XPS) and X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy. The size of PLLCQD was confirmed by HRTEM and AFM. The synthesized PLLCQD shows bright blue fluorescence and has a quantum yield of 19.35%. The highest emission band was observed at 471nm when excited to 370nm. The prepared PLLCQD exhibited excellent antibacterial activity against Escherichia coli and Staphylococcus aureus with inhibition zone 7-20 mm. The concentrations of 0.9 to 0.1gmL-1 were studied to determine minimum inhibitory concentration (MIC) by the agar well diffusion assay method. MIC of 0.2gml -1 concentration of PLLCQD is achieved. The anti-angiogenic activity of PLLCQD was determined using (Chick Chorioallantoic Membrane) CAM assay. CAM assay is a reliable in -vivo model to study angiogenesis also; many stimulators and inhibitors have been examined by this method. This study proves higher antibacterial efficiency of PLLCQD over non functionalized CQD. PLLCQD was successfully employed in bio-imaging of the bacterial cell through fluorescence microscopy. Further, PLLCQD displayed cytotoxic effect on endothelial cells and inhibited blood vessel formation in the CAM model.

Advantages of nanofibrous membranes for culturing of primary RPE cells compared to commercial scaffolds.

PURPOSE: Dysfunction of the retinal pigment epithelium (RPE) causes numerous forms of retinal degeneration. RPE replacement is a modern option to save vision. We aimed to test the results of transplanting cultured RPEs on biocompatible membranes. METHODS: We cultivated porcine primary RPE cells isolated from cadaver eyes from the slaughterhouse on two types of membranes: commercial polyester scaffolds Transwell (Corning Inc., Kenneburg, ME, USA) with 0.4 µm pore size and prepared Poly (L-lactide-co-DL-lactide) (PDLLA) nanofibrous membranes with an average pore size of 0.4 µm. RESULTS: Five types of assays were used for the analysis: immunocytochemistry (ICC), phagocytosis assay, Western blotting, real-time qPCR (RT-qPCR) and electron microscopy. RT-qPCR demonstrated that RPEs cultured on nanofibrous membranes have higher expressions of BEST1 (bestrophin 1), RLBP1 (retinaldehyde-binding protein 1), RPE65 (retinal pigment epithelium-specific 65 kDa protein), PAX6 (transcription factor PAX6), SOX9 (transcription factor SOX9), DCT (dopachrome tautomerase) and MITF (microphthalmia-associated transcription factor). ICC of the RPEs cultured on nanofibrous membranes showed more intensive staining of markers such as BEST1, MCT1 (monocarboxylate transporter 1), Na+ /K+ ATPase, RPE65 and acetylated tubulin in comparison with commercial ones. Additionally, the absence of α-SMA proved the stability of the RPE polarization state and the absence of epithelial-to-mesenchymal transition. RPE possessed high phagocytic activity. Electron microscopy of both membranes confirmed a confluent layer of RPE cells and their genuine morphological structure, which was comparable to native RPEs. CONCLUSIONS: Retinal pigment epitheliums cultured on polylactide nanofibrous membranes improved the final quality of the cell product by having better maturation and long-term survival of the RPE monolayer compared to those cultured on commercial polyester scaffolds. PDLLA-cultured RPEs are a plausible source for the replacement of non-functioning RPEs during cell therapy.

Advancement in Nanostructure-Based Tissue-Engineered Biomaterials for Retinal Degenerative Diseases.

The review intends to overview a wide range of nanostructured natural, synthetic and biological membrane implants for tissue engineering to help in retinal degenerative diseases. Herein, we discuss the transplantation strategies and the new development of material in combination with cells such as induced pluripotent stem cells (iPSC), mature retinal cells, adult stem cells, retinal progenitors, fetal retinal cells, or retinal pigment epithelial (RPE) sheets, etc. to be delivered into the subretinal space. Retinitis pigmentosa and age-related macular degeneration (AMD) are the most common retinal diseases resulting in vision impairment or blindness by permanent loss in photoreceptor cells. Currently, there are no therapies that can repair permanent vision loss, and the available treatments can only delay the advancement of retinal degeneration. The delivery of cell-based nanostructure scaffolds has been presented to enrich cell survival and direct cell differentiation in a range of retinal degenerative models. In this review, we sum up the research findings on different types of nanostructure scaffolds/substrate or material-based implants, with or without cells, used to deliver into the subretinal space for retinal diseases. Though, clinical and pre-clinical trials are still needed for these transplants to be used as a clinical treatment method for retinal degeneration.

Bioink: a 3D-bioprinting tool for anticancer drug discovery and cancer management.

'Bioinks' are important tools for the fabrication of artificial living-tissue constructs that are able to mimic all properties of native tissues via 3D bioprinting technologies. Bioinks are most commonly made by incorporating live cells of interest within a natural or synthetic biocompatible polymeric matrix. In oncology research, the ability to recreate a tumor microenvironment (TME) using by 3D bioprinting constitutes a promising approach for drug development, screening, and in vitro cancer modeling. Here, we review the different types of bioink used for 3D bioprinting, with a focus on its application in cancer management. In addition, we consider the fabrication of bioink using customized materials/cells and their properties in the field of cancer drug discovery.

Self-assembly of bovine serum albumin (BSA)-dextran bio-nanoconjugate: structural, antioxidant and in vitro wound healing studies.

Glycation of proteins is often considered as a method to improve their functional properties for promising applications in wound healing. Furthermore, a marked increase in percentage of radical scavenging activity of the conjugates makes it an effective antioxidant synthetic strategy. A simple conjugation process was employed to develop bovine serum albumin-dextran conjugates (BSA-dextran) using Maillard reaction. Higher electrophoretic mobility and surface charge in the prepared conjugates was observed in native PAGE electrophoresis and zeta potential. Moreover, the fluorescence, FTIR and Raman analysis of the BSA-dextran conjugates shows significant shift in the fluorescence and wavelength as a consequence of conjugate formation. In vitro wound healing assay showed increased cell proliferation and migration effect. These finding suggests that BSA-dextran conjugate could open up a new practical way for exploration in the area of wound healing.

Correction: Self-assembly of bovine serum albumin (BSA)-dextran bio-nanoconjugate: structural, antioxidant and in vitro wound healing studies.

[This corrects the article DOI: 10.1039/D0RA09301G.].