Doxorubicin conjugated AuNP/biopolymer composites facilitate cell cycle regulation and exhibit superior tumor suppression potential in KRAS mutant colorectal cancer

Colorectal cancer is a leading cause of death in the world. Despite the progress in therapeutic development, there are still challenges in clinical practice. Nanomedicine has emerged as a solution to enhance traditional therapy. Gold nanoparticles (AuNP) have been demonstrated as potential appliance in treating cancers, yet few studies investigated the capacity of biopolymer-conjugated AuNP in colon cancer as well as examined the system in both cancer cell line and animal models. In this study, we designed the AuNP/biopolymer composite therapeutic system with a chemotherapy agent, doxorubicin (DOX). Two composites with different drug load were applied (referred to as AuPPPyA and AuPPPyB). The composites were characterized by UV spectrum, transmission electron microscope (TEM), zeta potential measurement, and cell cycle analysis. Both therapeutic systems exhibited superior cytotoxic effects compared to DOX alone group. Compatible results were also demonstrated in vivo, as tumor inhibition rate were 46.2% in AuPPPyA and 66.4% in AuPPPyB, which were both higher than that of DOX alone (30%). Cell cycle regulation mediated by our composites was also examined in our study. In conclusion, our data demonstrated that AuNP/biopolymer composites are powerful in treating KRAS gene mutated colorectal cancer, and the system could potentially contribute to other clinical refractory diseases in the future.