Co-delivery nanosystem of Epigallocatechin Gallate and Rutin for anticancer and antibacterial activities

Abstract

Although chemotherapy has successfully treated cancer to some extent, high doses, multiple drug resistance, undesirable toxic effects, and non-selective targeting are the major pitfalls. Nano drug materials have emerged as a promising method to improve the therapeutic benefit for extremely hydrophobic drugs, and nano-based combination therapy can potentially target these challenges. Here, an amphiphilic PEG-PCL diblock copolymer co-encapsulated with epigallocatechin-3-gallate and rutin nanorods within the range of 110 ± 15 nm and 26 ± 5.3 nm in length and width was developed as a combination therapy that synergistically combines features of anticancer and antibacterial activities. The drug release kinetics revealed that drug release from nanorods is due to anomalous diffusion with 77% of EGCG and 62% of rutin at lower pH 5.0 for a time period of 24 h. In vitro cytotoxicity assays against A549 human lung adenocarcinoma and HeLa cervical cancer cell lines showed that nanorods have a concentration-dependent synergistic effect in inducing intracellular reactive oxygen species (ROS) generation and cancer cell apoptosis by the up-regulation of caspase 9/3 activities. Confocal laser scanning microscopy further confirmed the potential internalization of nanorods into the cancer cells. Also, nanorods showed antibacterial effects against E. coli and S. aureus strains by cell membrane damage confirmed by time-killing kinetic studies and SEM analysis. Besides, hemolytic studies showed the biocompatibility of nanorods with human red blood cells. These findings hold promise for engineering multifunctional nanorods-based co-delivery systems targeting cancer and bacterial infections.