Journal
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
Volume 179, Issue -, Pages 206-220Publisher
ELSEVIER
DOI: 10.1016/j.ejpb.2022.09.012
Keywords
Hepatocellular carcinoma (HCC); Nanovesicles; SP94 peptide; Sonodynamic therapy (SDT); Perfluorohexanes (PFH); Combination therapy
Categories
Funding
- National Natural Science Foundation of China [81671814]
- Heilongjiang Provincial Natural Science Foundation [ZD2016013]
- Training Project of Translation Medicine from Technology Innovation Center for Accurate Diagnosis and Treatment of Cold Land Diseases in Heilongjiang Province [CXZX-ZXKT02, CXZX-ZXKT03]
- Fundamental Research Funds for the Provincial Universities [JFQN202104, JFWLD202002, 2018XN22, 2018XN-24, JFXN201902, JFXN201908]
- Guiding project of Science and Technology from Science and Technology Bureau of Daqing City [zdy-2021-87, zdy-2019-87, zdy-2019-88]
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The novel oxygen self-enriched chemo/SDT nanocomposites significantly inhibited tumor growth by increasing oxygen levels and enhancing selectivity to liver tumor cells.
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.
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