Synthesis, characterization, and cytotoxicity assessment of biotinylated carbon dots nanoparticles as camptothecin delivery system

Abstract

Abstract Carbon dots (CDs) are one of the most highlighted carbon-based material for biological applications such as delivery of therapeutic payloads for cancer treatment mainly due to their excellent biocompatibility, low to no cytotoxicity, and unique optical properties. Camptothecin (CPT)-based drugs inhibit topoisomerase I, leading to destruction of DNA, and are currently being used clinically as important chemotherapeutic agents in treatment of cancer. However, different problems associated with cancer therapy hinder their anticancer activity. .In this work, we designed and synthesized two CPT prodrugs; compound I (CPT-biotin), compound II (CPT-CDs-biotin).\xa0 These compounds are designed to selectivity deliver the active drug to the vitamin receptors overexpressed on tumor cell surface by using biotin as a navigational molecule. The smooth drug release from compound I and II via glutathione-triggered self-immolation of the disulfide linker and CDs used as nanocarriers in compound II. In vitro drug release of nanoparticles demonstrated acceptable stability in phosphate buffer saline (PBS) containing 100 μM GSH at pH 7.4, the accumulative drug release approximately 17.6%. However, in 10 mM GSH medium reached to 84.9% in acetate buffer medium at pH 5.8. In vitro cytotoxicity study (MTT assay) demonstrated that compound I showed higher inhibition ratios on biotin receptor overexpressed cell lines (MCF-7, HepG2) and lower cytotoxicity on normal cell lines (CHO). Compound II showed good activity against (MCF-7, HepG2), and much lower cytotoxicity on (CHO).