Synthesis of highly fluorescent, amine-functionalized carbon dots from biotin-modified chitosan and silk-fibroin blend for target-specific delivery of antitumor agents.

Carbon dots (CDs) have been a promising theranostic tool with high biocompatibility and a tailorable fluorescence profile. Herein, we report the synthesis of highly fluorescent amine-functionalized CDs from low molecular weight chitosan (LMWC) and silk-fibroin (SF) blends. The synthesized CDs were quasi-spherical in shape with a size of 3 ± 1.5 nm. A significant increase in fluorescent intensity and quantum yield was achieved upon increasing the SF content due to nitrogen doping. For inducing target specificity to cancer cells, biotin was covalently conjugated to the CDs, and the conjugation was determined by FTIR spectroscopy. The conjugate was further loaded with 5-fluorouracil (5-FU) as a model anti-cancer drug. The MTT assay showed increased cytotoxicity of the conjugated CDs in cancer cells compared to normal cells. The live-cell imaging in MCF-7 cell lines showed bright blue-colored fluorescence and increased internalization of the conjugated CDs than the non-conjugate ones due to receptor-mediated endocytosis.

Synthesis of functionalized silk-coated chitosan-gold nanoparticles and microparticles for target-directed delivery of antitumor agents.

Chemically modified biopolymers derived nanomaterials have shown great potential in drug delivery and live-cell imaging. We have developed two materials, doxorubicin-loaded chitosan-gold nanoparticles and beads, both embedded with functionalized silk fibroin. Nanoparticles with size 8 ± 3 nm were synthesized using chitosan as reducing and stabilizing agent. Beads with 900-1000 µm size were formulated by the ionic gelation technique. Both the materials were coated with functionalized silk fibroin for targeted and sustained drug release properties. The coated materials showed retarded drug release compared to the uncoated ones. The cytotoxicity was assessed in HeLa cell lines, which demonstrated a maximum dose-dependent decrease in cell viability for the cells treated with folate conjugated silk fibroin coated nanoparticles. The live-cell imaging of the nanoparticles unveiled the increased cellular uptake of the coated materials by seven folds than the uncoated ones. Thus, functionalized silk coated materials can be effective drug delivery tools for targeted and sustained drug release.

Development of a photoresponsive chitosan conjugated prodrug nano-carrier for controlled delivery of antitumor drug 5-fluorouracil.

Controlled drug delivery offers improved therapeutic efficacy of the drugs while minimizing side effects. Biocompatible polymers and nanomaterials have emerged as effective carriers for the controlled delivery of drugs. We have synthesized a prodrug of 5-fluorouracil (5FU) covalently conjugated to low molecular weight chitosan (LMWC) via a photocleavable linker. The conjugate was designed to be cleaved under 365 nm UV-A radiations, which is regarded as relatively safe for the cells and release 5FU in a dose-dependent manner. The conjugate showed enhanced water solubility compared to LMWC and forms hydrogel and DMSO gel. The conjugate polymer was also fabricated into nanoparticles by ionic gelation technique. The size of the nanoparticles was found to be in the range 70-90 nm, thus should have the ability to penetrate into living cells. In vitro release study of 5FU from the conjugate showed controlled release of the antitumor drug over time. The synthesized nanoparticles and the gel, therefore, could be a good model for controlled release of antitumor drugs.