Xiao Su1, Hao Song1,2,3, Fangfang Niu1, Kaixuan Yang1, Geng Kou1,2, Xiaohang Wang4, Huaiwen Chen1, Wei Li1,2, Shangjing Guo2, Jun Li2, Bohua Li1,2, Si-Shen Feng1,5,6, Jianxin Jiang7, Chuan Yin4, Jie Gao1,2,8. 1. International Joint Cancer Institute, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China. 2. College of Pharmacy, Liaocheng University, 1 Hu'nan Road, Liaocheng, Shandong 25200, PR China. 3. Centre for Stem Cell & Regenerative Medicine, Liaocheng People's Hospital, 67 Dongchang West Road, Liaocheng, Shangdong 252000, China. 4. Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China. 5. Department of Chemical & Biomolecular Engineering, National University of Singapore, Block E5, 02-11, 4 Engineering Drive 4, Singapore 117576, Singapore. 6. Suzhou NanoStar Biopharm Inc Ltd, BioBay, Bld B2, Unit 604, 218 Xing-Hu Street, Suzhou Industrial Park, Suzhou 215123, China. 7. Department of Hepatobiliary Surgery, Hubei Province Tumor Hospital, Wuhan, Hubei 430079, China. 8. Department of Pharmaceutical Sciences, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
Abstract
AIM: To develop novel nanoliposomes (Lip-ADR-Cer) codelivering doxorubicin (ADR) and PEGylated C16 ceramide (PEG-ceramide C16) to overcome multidrug resistance. MATERIALS & METHODS: The antitumor activity and mechanism of Lip-ADR-Cer were evaluated. RESULTS & CONCLUSION: The IC50 of Lip-ADR-Cer after 48-h treatment with the MCF-7/ADR and HL-60/ADR cancer cells, both being ADR resistant, was 2.2- and 1.4-fold effective respectively versus the general nanoliposomes with no PEG-ceramide C16 (Lip-ADR). The antitumor assay in mice bearing MCF-7/ADR or HL-60/ADR xenograft tumors confirmed the superior antitumor activity of Lip-ADR-Cer over Lip-ADR. We found that the improved therapeutic effect of Lip-ADR-Cer may be attributed to both of the cytotoxic effect of PEG-ceramide C16 and glucosylceramide synthase overexpression in multidrug resistance cells.
AIM: To develop novel nanoliposomes (Lip-ADR-Cer) codelivering doxorubicin (ADR) and PEGylated C16 ceramide (PEG-ceramide C16) to overcome multidrug resistance. MATERIALS & METHODS: The antitumor activity and mechanism of Lip-ADR-Cer were evaluated. RESULTS & CONCLUSION: The IC50 of Lip-ADR-Cer after 48-h treatment with the MCF-7/ADR and HL-60/ADR cancer cells, both being ADR resistant, was 2.2- and 1.4-fold effective respectively versus the general nanoliposomes with no PEG-ceramide C16 (Lip-ADR). The antitumor assay in mice bearing MCF-7/ADR or HL-60/ADR xenograft tumors confirmed the superior antitumor activity of Lip-ADR-Cer over Lip-ADR. We found that the improved therapeutic effect of Lip-ADR-Cer may be attributed to both of the cytotoxic effect of PEG-ceramide C16 and glucosylceramide synthase overexpression in multidrug resistance cells.