SP94-Targeted Nanoparticles Enhance the Efficacy of Sorafenib and Improve Liver Cancer Cell Discrimination
Meenu Chopra, Agustin Sgro, Marck Nörret, Pilar Blancafort, K. Swaminathan Iyer, Cameron W. Evans
Abstract
The cell type-targeted delivery of chemotherapeutic drugs together with minimizing potential side effects or toxicity are key bottlenecks for the clinical treatment of unresectable hepatocellular carcinoma (HCC). Current treatment of HCC relies on multikinase inhibitors such as sorafenib, which has provided limited survival benefits associated with recurrence or disease resistance. Here, we report a highly specific nanocarrier derived from poly(glycidyl methacrylate) (PGMA) for efficient delivery of sorafenib in liver cancer cells. To achieve cancer-specific cell delivery, PGMA nanoparticles were conjugated with an HCC-targeting peptide, SP94. The resulting HCC-specific PGMA nanoparticles encapsulating sorafenib exhibited a sustained release profile of sorafenib, HCC-specific uptake, and reduced nonspecific uptake in normal hepatocytes. Our results showed that SP94-sorafenib nanoparticles enhanced the therapeutic efficacy of sorafenib in a highly selective manner in HCC cells with negligible uptake in normal hepatocytes. The delivery system reported here has the potential for enhancing the therapeutic index of chemotherapies while minimizing side effects and toxicities in HCC patients.