Cabozantinib Encapsulated Lipid and Polymeric Nanoparticles: In-depth Exploration of Molecular Interactions, Formulation Strategies, and In vitro Studies on Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC), a prime liver cancer with a high global mortality rate, has prompted the exploration of innovative therapeutic strategies, such as nanomedicine-based anticancer agents, due to the limitations of conventional chemotherapy. This study aimed to identify the most effective molecule through molecular-level interaction studies with three key anticancer pathway proteins. The selected molecule was then encapsulated with both polymer and lipid to create nanoparticles, and in vitro studies on HCC were conducted to assess its activity. The results of the interaction analysis revealed that Cabozantinib exhibited strong binding affinity with three proteins—folate receptor (5IZQ), vascular endothelial growth factor (5ABD), and CD44 (4PZ3)—with energies of -39.3697, -44.4525 kcal/mol, and -44.5276 kcal/mol, respectively. In the formulated nanoparticles, Cabozantinib-loaded lipid nanoparticles demonstrated higher encapsulation efficacy and drug-loading efficiency compared to their polymeric nanoformulations. In vitro cytotoxicity investigations indicated that Cabozantinib-loaded lipid nanoparticles displayed superior anticancer efficacy, with an IC50 value of 100.55 ± 0.05 µg/mL, as opposed to 140.65 ± 0.05 µg/mL for Cabozantinib-loaded polymeric nanoparticles against Hep3B cell lines. Additionally, fluorescence-based screening studies further affirmed the remarkable anticancer potential of Cabozantinib-loaded lipid nanoparticles, primarily through the induction of apoptosis in Hep3B cells. These findings suggest that Cabozantinib-loaded lipid nanoparticles hold promise as nanoformulations for targeting HCC.