Integrated platform of oxygen self-enriched nanovesicles: SP94 peptide-directed chemo/sonodynamic therapy for liver cancer

Hepatocellular carcinoma (HCC) is a most common primary liver cancer among the most deadly malignancies. Selectively killing the cancer cells within the liver urgently requires the novel treatment strategies. The com-bination of sonodynamic therapy (SDT) and chemotherapy based on the nanotechnology have achieved some achievements in the HCC treatments. However, off-targeting drug delivery to healthy cells and the hypoxic microenvironment in the solid tumors frustrate the efforts to the combined strategy. The hypoxic microenvi-ronment restrains the generation of ROS, leading to the decreased effects of SDT. To improve the clinical out-comes of chemo/SDT strategy, we created a novel oxygen self-enriched active targeted nanovesicle (ICG-DOX NPs/PFH@SP94-Lip). SP94 peptide could enhance the selectivity of the nanovesicles to liver tumor cells rather than normal liver cells. Besides, an oxygen carrier, perfluorohexanes (PFH), was co-loaded into liposomes to increase the oxygen level in tumor tissue, thus improving the effects of SDT. The in vivo studies showed that the ICG-DOX NPs/PFH@SP94-Lip combined with the external US stimulation significantly inhibited effects on tumor growth. Therefore, this novel oxygen self-enriched chemo/SDT nanocomposites represents a proof-of-concept liver tumor treatment strategy.