Dual-Functional Liposomes with Carbonic Anhydrase IX Antibody and BR2 Peptide Modification Effectively Improve Intracellular Delivery of Cantharidin to Treat Orthotopic Hepatocellular Carcinoma Mice
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-09-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/24/18/3332 |
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| author | Xue Zhang Congcong Lin Waikei Chan Kanglun Liu Aiping Lu Ge Lin Rong Hu Hongcan Shi Hongqi Zhang Zhijun Yang |
| author_facet | Xue Zhang Congcong Lin Waikei Chan Kanglun Liu Aiping Lu Ge Lin Rong Hu Hongcan Shi Hongqi Zhang Zhijun Yang |
| author_sort | Xue Zhang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T23:27:51Z |
| format | Article |
| id | doaj.art-aece87c793f643c7af7e44299979226e |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-11T23:27:51Z |
| publishDate | 2019-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-aece87c793f643c7af7e44299979226e2022-12-22T03:57:16ZengMDPI AGMolecules1420-30492019-09-012418333210.3390/molecules24183332molecules24183332Dual-Functional Liposomes with Carbonic Anhydrase IX Antibody and BR2 Peptide Modification Effectively Improve Intracellular Delivery of Cantharidin to Treat Orthotopic Hepatocellular Carcinoma MiceXue Zhang0Congcong Lin1Waikei Chan2Kanglun Liu3Aiping Lu4Ge Lin5Rong Hu6Hongcan Shi7Hongqi Zhang8Zhijun Yang9Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou 225001, ChinaSchool of Chinese Medicine, Hong Kong Baptist University, Hong Kong, ChinaSchool of Chinese Medicine, Hong Kong Baptist University, Hong Kong, ChinaSchool of Chinese Medicine, Hong Kong Baptist University, Hong Kong, ChinaSchool of Chinese Medicine, Hong Kong Baptist University, Hong Kong, ChinaSchool of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong, ChinaInstitute of Translational Medicine, Medical College, Yangzhou University, Yangzhou 225001, ChinaInstitute of Translational Medicine, Medical College, Yangzhou University, Yangzhou 225001, ChinaSchool of Chinese Medicine, Hong Kong Baptist University, Hong Kong, ChinaSchool of Chinese Medicine, Hong Kong Baptist University, Hong Kong, ChinaLiposomal 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.https://www.mdpi.com/1420-3049/24/18/3332hepatocellular carcinomadual-functionalized liposomescarbonic anhydrase IXBR2 peptidecantharidin |
| spellingShingle | Xue Zhang Congcong Lin Waikei Chan Kanglun Liu Aiping Lu Ge Lin Rong Hu Hongcan Shi Hongqi Zhang Zhijun Yang Dual-Functional Liposomes with Carbonic Anhydrase IX Antibody and BR2 Peptide Modification Effectively Improve Intracellular Delivery of Cantharidin to Treat Orthotopic Hepatocellular Carcinoma Mice Molecules hepatocellular carcinoma dual-functionalized liposomes carbonic anhydrase IX BR2 peptide cantharidin |
| title | Dual-Functional Liposomes with Carbonic Anhydrase IX Antibody and BR2 Peptide Modification Effectively Improve Intracellular Delivery of Cantharidin to Treat Orthotopic Hepatocellular Carcinoma Mice |
| title_full | Dual-Functional Liposomes with Carbonic Anhydrase IX Antibody and BR2 Peptide Modification Effectively Improve Intracellular Delivery of Cantharidin to Treat Orthotopic Hepatocellular Carcinoma Mice |
| title_fullStr | Dual-Functional Liposomes with Carbonic Anhydrase IX Antibody and BR2 Peptide Modification Effectively Improve Intracellular Delivery of Cantharidin to Treat Orthotopic Hepatocellular Carcinoma Mice |
| title_full_unstemmed | Dual-Functional Liposomes with Carbonic Anhydrase IX Antibody and BR2 Peptide Modification Effectively Improve Intracellular Delivery of Cantharidin to Treat Orthotopic Hepatocellular Carcinoma Mice |
| title_short | Dual-Functional Liposomes with Carbonic Anhydrase IX Antibody and BR2 Peptide Modification Effectively Improve Intracellular Delivery of Cantharidin to Treat Orthotopic Hepatocellular Carcinoma Mice |
| title_sort | dual functional liposomes with carbonic anhydrase ix antibody and br2 peptide modification effectively improve intracellular delivery of cantharidin to treat orthotopic hepatocellular carcinoma mice |
| topic | hepatocellular carcinoma dual-functionalized liposomes carbonic anhydrase IX BR2 peptide cantharidin |
| url | https://www.mdpi.com/1420-3049/24/18/3332 |
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