Dual-Functional Liposomes with Carbonic Anhydrase IX Antibody and BR2 Peptide Modification Effectively Improve Intracellular Delivery of Cantharidin to Treat Orthotopic Hepatocellular Carcinoma Mice
Publication in refereed journal

香港中文大學研究人員
替代計量分析
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其它資訊
摘要Liposomal nanotechnology has a great potential to overcome the current major problems of chemotherapy. However, the lack of penetrability and targetability retards the successful delivery of liposomal carriers. Previously, we showed that BR2 peptide modification endowed cantharidin-loaded liposomes with intracellular penetration that enhanced the drug cytotoxic effects. Here, we aimed to improve the targeting delivery of drugs into cancer cells via highly expressed carbonic anhydrase IX (CA IX) receptors by modifying our previous catharidin-loaded BR2-liposomes with anti-CA IX antibody. A higher cellular uptake of dual-functional liposomes (DF-Lp) than other treatments was observed. Induction of CA IX over-expressing resulted in a higher cellular binding of DF-Lp; subsequently, blocking with excess antibodies resulted in a decreased cancer-cell association, indicating a specific targeting property of our liposomes towards CA IX expressed cells. After 3h tracking, most of the liposomes were located around the nucleus which confirmed the involvement of targeting intracellular delivery. Cantharidin loaded DF-Lp exhibited enhanced cytotoxicity in vitro and was most effective in controlling tumor growth in vivo in an orthotopic hepatocellular carcinoma model compared to other groups. Collectively, our results presented the advantage of the BR2 peptide and CA IX antibody combination to elevate the therapeutic potential of cantharidin loaded DF-liposomes.
著者Xue ZHANG, Congcong LIN, Waikei CHAN, Kanglun LIU, Aiping LU, Ge LIN, Rong HU, Hongcan SHI, Hongqi ZHANG, Zhijun YANG
期刊名稱Molecules
出版年份2019
月份9
卷號24
期次18
出版社MDPI
文章號碼3332
國際標準期刊號1420-3049
語言英式英語
關鍵詞hepatocellular carcinoma, dual-functionalized liposomes, carbonic anhydrase IX, BR2 peptide, cantharidin
Web of Science 學科類別Biochemistry & Molecular Biology;Chemistry, Multidisciplinary;Biochemistry & Molecular Biology;Chemistry

上次更新時間 2021-17-09 於 00:11