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Hyaluronic Acid Coated and Poly-L-lysine Functionalized Graphene Quantum Dots for CD44 targeted Anti-Cancer Drug Delivery against Osteosarcoma

Khushboo Dutta1,2, Saty Decakash Ahirwar2, Vijay Kumar Thakur3,4,5, Piyush Kumar Gupta6*, Sunita Nayak1,2*

Due to less toxicity and strong fluorescence properties, graphene quantum dots, i.e., GQDs have been shown to play a promising role in drug delivery applications. Hyaluronic acid (HA), used as a targeting ligand in this drug delivery system, is a polysaccharide which interacts with the hyaluronan receptor that is, CD44. Poly-L-lysine (PLL), containing amine groups, can be efficiently conjugated to the hydrophobic substances with carboxyl moieties. In this study, a novel drug delivery system composed of GQD coated with HA and coupled with PLL has been designed as a potent theranostic candidate for osteosarcoma therapy for the targeted delivery of DNA intercalating drug doxorubicin (DOX) to cancer cells. The characterization studies for morphology, structural analysis, and optical properties were evaluated. The drug loading, drug release profile, and anti-cancer effect of the GQDs-HA-PLL-DOX were investigated. The GQDs being synthesized have relatively narrow size distribution, with a diameter less than 5 nm. The maximum loading efficiency of the drug was achieved at 66% and pH-responsive drug release achieved was as high as 50%. The in vitro results showed good biocompatibility of GQD-conjugates. Fluorescence microscopy assay showed a fast and marked uptake of the drug with the time course. Hence, this system finds potential applications for in vitro cell imaging and targeted cancer therapy.

Keywords

Graphene quantum dot; Osteosarcoma; Targeted delivery; Anti-cancer activity; Fluorescence

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