Abstract
Nanoparticles (NPs) are ideal candidates for safe, directed and effective delivery of chemotherapeutic agents to cancer cells. Herein, we report the synthesis of a gold NP (GNP) based delivery system as a platform for doxorubicin (DOX) delivery to cancer cells. GNPs synthesized by citrate reduction of the gold salt was used to encapsulate DOX, using sodium tripolyphosphate (TPP) as a linking agent. The subsequent functionalization of the DOX-GNP with chitosan (CS) and folate-linked chitosan (F-CS) resulted in the formation of CS-GNP-DOX and F-CS-GNP-DOX delivery systems. The synthesized DOX nanocarriers were characterized using UV–visible and ATR-FTIR spectroscopy, transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Drug release and kinetic evaluations were done in simulated tumour and physiological microenviroments. The drug-nanocomplexes were evaluated in an in vitro MTT assay for their effect on cell proliferation with further assessments on the mechanisms associated with the toxicity. The NPs and nanocomplexes were spherically shaped, colloidally stable, and displayed a pH-dependent DOX release that closely followed a first or zero-order kinetic model. CS-GNP-DOX and F-CS-GNP-DOX displayed higher chemotherapeutic activity in the human breast (MCF-7), cervical (HeLa) and hepatocellular (HepG2) carcinoma cell lines when compared to free DOX. The lowest IC50 obtained for CS-GNP-DOX and F-CS-GNP-DOX in the cancer cells was significantly lower than that for free DOX. The F-CS-GNP-DOX nanocomplex displayed superior anticancer effects over CS-GNP-DOX in the breast and cervical cancer cells, predominantly due to enhanced cellular uptake via their over-expressed folate receptors (FRα). These nanocomplexes also induced mitochondrial membrane depolarization and activated downstream caspases during apoptotic induction in the breast and cervical cancer cells. Overall, these DOX-nanocomplexes have the potential for clinical application and are be promising lead candidates for further development.
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