Co-Delivery of Doxorubicin and PEGylated C16-Ceramide by Nanoliposomes for Enhanced Therapy Against Multidrug Resistance

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

Financial & competing interests disclosure

This work was financially supported by the National Natural Science Foundation of China (project number: 81472829, 81402512), Shanghai Young Rising Star of Science (project number: 12QB1402400), Shanghai Chen’guang Scholar Funding, Ministry of Science and Technology of China (973 & 863 program projects, project number: 2012AA020809), National Key Project for Infectious Diseases (2012ZX10002012-009), Pudong New Area Science and Technology Commission of and a special grant from the Ministry of Education of China (Key Laboratory) and the Shanghai Commission of Education and National Special Projects for New Drug Development and Infectious Diseases. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This work was financially supported by the National Natural Science Foundation of China (project number: 81472829, 81402512), Shanghai Young Rising Star of Science (project number: 12QB1402400), Shanghai Chen’guang Scholar Funding, Ministry of Science and Technology of China (973 & 863 program projects, project number: 2012AA020809), National Key Project for Infectious Diseases (2012ZX10002012-009), Pudong New Area Science and Technology Commission of and a special grant from the Ministry of Education of China (Key Laboratory) and the Shanghai Commission of Education and National Special Projects for New Drug Development and Infectious Diseases. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.