Co-delivery of doxorubicin and PEGylated C16-ceramide by nanoliposomes for enhanced therapy against multidrug resistance

  • Nanomedicine (Lond). 2015;10(13):2033-50. doi: 10.2217/nnm.15.50.
Xiao Su  1 ,  Hao Song  1  2  3 ,  Fangfang Niu  1 ,  Kaixuan Yang  1 ,  Geng Kou  1  2 ,  Xiaohang Wang  4 ,  Huaiwen Chen  1 ,  Wei Li  1  2 ,  Shangjing Guo  2 ,  Jun Li  2 ,  Bohua Li  1  2 ,  Si-Shen Feng  1  5  6 ,  Jianxin Jiang  7 ,  Chuan Yin  4 ,  Jie Gao  1  2  8
Affiliations
  • 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.
PMID: 26084553 DOI: 10.2217/nnm.15.50
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.

Keywords
cancer nanotechnology; glucosylceramide synthase; molecular biomaterials; multidrug resistance; nanomedicine; pharmaceutical nanotechnology.
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