Celastrol-Loaded Hyaluronic Acid/Cancer Cell Membrane Lipid Nanoparticles for Targeted Hepatocellular Carcinoma Prevention.

Abstract

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide, and its prevention and treatment face severe challenges. It is crucial to improve the targeting of drugs on tumor cells and tissues. Celastrol (CeT), as an active ingredient of traditional Chinese medicine, possesses strong antitumor effects, especially in triggering apoptosis of HCC. However, due to its toxicity and lack of targeting, its application is greatly limited. HMCLPs, a nano-biomimetic platform carrying CeT with controllable drug release, enhanced targeting, and immunocompatibility, were developed for the first time, which can be used for the treatment of HCC. By utilizing homologous cell membranes and hyaluronic acid (HA), HMCLPs can precisely target tumor regions and release CeT in a controlled manner. Both in vitro and in vivo studies have demonstrated that HMCLPs loaded with CeT significantly increased the accumulation of reactive oxygen species (ROS), induced mitochondrial damage, and triggered apoptosis of HCC cells, resulting in effective treatment with minimal adverse reaction. The development of HMCLPs as a nanocarrier system for CeT delivery offers a promising therapeutic strategy for HCC. This innovative approach improves the targeted delivery and bioavailability of CeT, dramatically induces apoptosis in HCC cells, and exerts its powerful antitumor effects while minimizing systemic toxicity. The present study highlights the potential of combining innovative nanocarriers with powerful natural compounds such as CeT to enhance efficacy and reduce toxicity.