Abstract
Despite of the remarkable cytotoxic and imaging potential of ultra-small metal nanoclusters, their toxicity-free and targeted delivery to cancerous cells remains a substantial challenge that hinders their clinical applications. In this study, a polymeric scaffold was first synthesized by grafting folic acid and thiol groups to chitosan (CS) for cancer cell targeting and improved gastric permeation. Furthermore, silver nanocluster (Ag NCs) were synthesized in situ, within CS scaffold by microwave irradiation and core-shell nanocapsules (NCPs) were prepared with hydrophobic docetaxel (DTX) in the core and Ag NCs embedded CS in the shell. A significant cytotoxicity synergism (~300 folds) was observed for DTX with co-delivery of Ag NCs against breast cancer MDA-MB-231 cells. Following oral administration, the DTX-Ag-NCPs increased bioavailability due to enhanced drug transport across gut (9 times), circulation half-life (~6.8 times) and mean residence time (~6.7 times), as compared to the control DTX suspension. Moreover, 14 days acute oral toxicity of the DTX-Ag-NCPs was performed in mice and evaluated for changes in blood biochemistry parameters, organ to body weight index and histopathology of liver and kidney tissues that revealed no significant evidence of toxicity suggesting the safety and efficiency of the DTX-Ag-NCPs as hybrid nanocarrier for biocompatible delivery of metal nanoclusters.
Highlights
Nanotechnology is an emerging field in medical sciences enabling the use of nanoscale metallic, polymeric materials or their composites for various biomedical applications
Stabilized Ag NCs with blue fluorescence were synthesized via microwave assisted method
Ag was able to be reduced inside the thiol pockets of branched CS polymer which was subsequently used for the DTX-Ag-NCPs preparation (Fig. 1)
Summary
Nanotechnology is an emerging field in medical sciences enabling the use of nanoscale metallic, polymeric materials or their composites for various biomedical applications. Metal based drug nanocarriers have evolved as efficient therapeutic moieties with diverse potentials For this purpose, metal nanoparticles including gold (Au), silver (Ag), iron oxide (Fe) and zinc oxide (ZnO) have shown tremendous potential in therapeutics (anti-bacterial, anti-fungal and anti-cancer) and diagnostics (MRI, PET, SPECT, Fluorescent NCs, quantum dots) application[2,3,4,5,6]. Metal nanoparticles including gold (Au), silver (Ag), iron oxide (Fe) and zinc oxide (ZnO) have shown tremendous potential in therapeutics (anti-bacterial, anti-fungal and anti-cancer) and diagnostics (MRI, PET, SPECT, Fluorescent NCs, quantum dots) application[2,3,4,5,6] Among these nanomaterials, nanoparticles and complexes of Ag are known for having antimicrobial and cytotoxic effects since decades[7]. These hybrid nanocapsules were evaluated for acute oral toxicity to establish a broader picture of the DTX-Ag-NCPs as drug carrier (Fig. 1)
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