Journal
MACROMOLECULAR BIOSCIENCE
Volume 14, Issue 10, Pages 1415-1428Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/mabi.201400149
Keywords
Doxorubicin; intracellular drug release; nanomicelles; redox-responsive; vitamin E succinate
Funding
- National Nature Science Foundation of China [81173008, 81273450, 81373336]
- Program for New Century Excellent Talents in University [NCET-12-1015]
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A redox-responsive poly(ethylene glycol) (PEG)-sheddable copolymer of disulfide-linked PEG 5000-lysine-di-tocopherol succinate (P5kSSLV) is developed which can self-assemble into nanomicelles in aqueous condition and trigger the rapid release of encapsulated drugs within tumor cells. The reduction-insensitive doxorubicin (DOX)-loaded P5kLV (P5kLV-DOX) nanomicelles are further prepared. Then head-to-head comparison of P5kSSLV-DOX, P5kLV-DOX and DOX-Sol is performed concerning in vitro release, cytotoxicity, cellular uptake and apoptosis. Results show that P5kSSLV-DOX nanomicelles have a faster DOX release, a higher anti-tumor activity and more DOX concentrating in the nucleus than P5kLV-DOX nanomicelles. In conclusion, the redox-responsive P5kSSLV nanomicelles might hold a great potential to improve chemotherapy by tumor-triggering intracellular rapid release. The outcomes of this study also address the significance of such head-to-head comparison studies in translational research of nanomedicine.
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