Fabrication of hyaluronic acid with graphene quantum dot as a dual drug delivery system for cancer therapy

Abstract

With recent advancements in nanomedicine, there has been growing interest in developing drug delivery systems with multifunctional capabilities. In this study, we developed a novel dual drug delivery system by combining two drug carriers via positive and negative electrostatic interactions. First, we modified polyethyleneimine (PEI) with graphene quantum dots (GQDs) to create a positively charged particle (GPI) with high drug loading efficiency and good dispersibility. Second, we embedded the pyrenebutyric acid structure in hyaluronic acid (HA) through EDC/NHS cross-linking and used TAK-632 as the hydrophobic drug to create negatively charged particles (HANPs) with hydrogel-like properties and the CD44 receptor. After the two components were constructed, the increase in the particle charge and simultaneous delivery of both drugs synergistically enhanced the therapeutic effect of this strategy. Qualitative tests confirmed the successful synthesis of the drug carrier, while the potential of this system as a cancer treatment strategy was evaluated in HCT116 cancer cells (through MTT cell viability assays) and in vivo mice xenograft experiments. Our results demonstrated that the dual drug delivery system, HANPs(TAK)/GPI(DOX), had a significant inhibitory effect on the growth of cancer cells both in vitro and in vivo, suggesting that this system is a promising candidate for a new type of treatment.