Engineered tumor microvesicles modified by SP94 peptide for arsenic trioxide targeting drug delivery in liver cancer therapy

Abstract

Liver cancer is among the leading cause of cancer related death worldwide. There is growing interest in using traditional Chinese medicines such as arsenic trioxide (ATO) to treat liver cancer. ATO have attracted attention due to its wide range of anti-cancer activities. However, the current ATO formulations are associated with drawbacks such as short half-life, lack of targeting ability towards solid tumors and apparent toxic side effects. Tumor microvesicles (TMVs) has shown encouraging results for the delivery of drugs to solid tumor. In this work, we designed ATO loaded TMVs further modified by SP94 peptide as liver cancer specific ligand (ATO@SP94-TMVs). This drug delivery system utilized SP94 peptide that selectively targets liver cancer cells while TMVs increase the accumulation of ATO at tumor site and activate immune response owing to the associated antigens. ATO@SP94-TMVs exhibited high encapsulation efficiency and tumor microenvironment triggered enhanced release of ATO in vitro. Cytotoxicity and uptake studies revealed remarkable inhibition and specific targeting of H22 cells. In addition, excellent immune response was detected in vitro, enhancing anti-tumor efficacy. Furthermore, a tumor inhibition rate of about 53.23 % was observed in H22 bearing tumor model. Overall, these results confirm that ATO@SP94-TMVs can be a promising nano drug delivery system for the future liver cancer therapy and improve its clinical applications.