期刊
NANOMEDICINE
卷 10, 期 13, 页码 2033-2050出版社
FUTURE MEDICINE LTD
DOI: 10.2217/NNM.15.50
关键词
cancer nanotechnology; glucosylceramide synthase; molecular biomaterials; multidrug resistance; nanomedicine; pharmaceutical nanotechnology
资金
- National Natural Science Foundation of China [81472829, 81402512]
- Shanghai Young Rising Star of Science [12QB1402400]
- Shanghai Chen'guang Scholar Funding, Ministry of Science and Technology of China (973 program project) [2012AA020809]
- Shanghai Chen'guang Scholar Funding, Ministry of Science and Technology of China (863 program project) [2012AA020809]
- National Key Project for Infectious Diseases [2012ZX10002012-009]
- Pudong New Area Science and Technology Commission of Ministry of Education of China (Key Laboratory)
- Ministry of Education of China (Key Laboratory)
- Shanghai Commission of Education
- National Special Projects for New Drug Development and Infectious Diseases
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.
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