Targeted Nanotherapy by Vinblastine-Loaded Chitosan-Coated PLA Nanoparticles to Improve the Chemotherapy via Reactive Oxygen Species to Hamper Hepatocellular Carcinoma

Liver cancer is a prevalent and significant cause of death in humans. The use of novel biodegradable materials for various biomedical applications is being recently recommended as complementary as well as alternative solution for traditional chemotherapy. This study focuses on the synthesis of biodegradable nanocarriers [chitosan-coated poly(lactic acid) NPs (Cht-PLA NPs)] for the delivery of an anticancer drug vinblastine (Vbx) and to evaluate its therapeutic potential in human hepatocellular carcinoma (HepG2) cells. The Cht-PLA NPs were synthesized using the nanoprecipitation method and characterized by transmission electron microscopy, scanning electron microscopy, Fourier transform infrared spectroscopy, dynamic light scattering, and zeta potential techniques. The results showed that the nanoparticle sizes are in the range of 100-200 nm with positive surface charge. The release profile of the synthesized nanoformulation showed controlled release of the Vbx drug for 72 h. The anticancer efficacy of the synthesized nanoformulation was assessed on the HepG2 cell lines. The <i>in vitro</i> cytotoxicity study revealed that the Vbx-loaded Cht-PLA NPs showed higher toxicity with an increase in concentration as compared to the Vbx alone. Additionally, an <i>in vitro</i> cellular uptake study revealed higher internalization as compared to the drug alone due to the chitosan coating. Further, the ability to stimulate the reactive oxygen species (ROS) generation and variation in mitochondrial membrane potential at the IC₅₀ concentration of Vbx-loaded Cht-PLA NPs was confirmed by using 2,7-dichlorodihydrofluorescein diacetate and rhodamine 123 dyes, respectively, and were analyzed under fluorescence microscopy. Hence, the results showed that Vbx-loaded Cht-PLA NPs possess high anticancer activity due to its higher cellular toxicity, cellular uptake, increased ROS production, and disruption in mitochondrial membrane potential. All these properties of the synthesized nanoformulation suggest it's potential applications in drug delivery systems, targeting liver cancer.