Star-Shape Redox-Responsive PEG-Sheddable Copolymer of Disulfide-Linked Polyethylene Glycol-Lysine-di-Tocopherol Succinate for Tumor-Triggering Intracellular Doxorubicin Rapid Release: Head-to-Head Comparison

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.