Self-assembled carrier-free drug nanoparticles for enhanced synergistic therapy of liver cancer

Abstract

Carrier-free nanodrug delivery systems, composed entirely of active drug molecules, represent a sustainable approach for next-generation nanodrug technologies.This study utilizes hydroxycamptothecin (HCPT), curcumin (CUR), and glycyrrhizic acid (GA) to construct a ternary, carrier-free self-assembled nanoparticle system (GA/CUR/HCPT-NPs). It investigates the in vivo transport processes in cells and animals, evaluates the synergistic anti-liver cancer efficacy, and assesses toxicity in both in vivo and in vitro models. The findings provide valuable insights for the development of carrier-free, green nanodrug delivery systems. Molecular dynamics (MD) simulation snapshots confirmed that GA, CUR, and HCPT molecules associate through intermolecular forces, including van der Waals interactions and hydrogen bonding. The GA/CUR/HCPT-NPs had a size of 146.37 ± 0.157 nm, a polydispersity index (PDI) of 0.157 ± 0.010, and a zeta potential of −34.43 ± 0.771 mV, indicating good stability during storage at 4 °C for 7 days. Compared to the single-drug group and the physical mixture, GA/CUR/HCPT-NPs significantly enhanced cytotoxicity and uptake efficiency in Huh7 and BEL-7404 liver cancer cells. Additionally, GA/CUR/HCPT-NPs exhibited strong synergistic anti-liver cancer effects in vivo and in vitro, without notable liver or kidney toxicity. Thus, carrier-free ternary nanoparticles, prepared using a simple and effective green strategy, offer promising strategy for combination antitumor therapy.