Poly(ethylene glycol)-sheddable reduction-sensitive polyurethane micelles for triggered intracellular drug delivery for osteosarcoma treatment

作者：Zhengjie Yang, Qianping Guo, Yan Cai, Xuesong Zhu, Caihong Zhu, Yuling Li, Bin Li · 发表于：Journal of Orthopaedic Translation · 年份：2019 · DOI：10.1016/j.jot.2019.11.001 · 被引用次数：22 · 研究领域：Nanoparticle-Based Drug Delivery、Polymer Surface Interaction Studies、Nanoplatforms for cancer theranostics

BACKGROUND: The survival rate of osteosarcoma therapy still lags behind overall cancer therapies due to the intrinsic or acquired drug resistance. Developing novel drug delivery systems that may overcome drug resistance would greatly facilitate osteosarcoma therapy. METHODS: Poly(ethylene glycol) (PEG)-sheddable reduction-sensitive polyurethane (SS-PU-SS-PEG) was synthesized using a disulfide-containing polycaprolactone diol as the hydrophobic block and a cystamine-functionalized PEG as the hydrophilic block. SS-PU-SS-PEG micelles were then prepared to load the anti-tumor drug Doxorubicin (DOX) in order to achieve triggered intracellular drug delivery to improve the efficacy of osteosarcoma therapy. RESULTS: When DOX was used as a model drug, the drug-loaded SS-PU-SS-PEG micelles were about 82∼94 nm in diameter and exhibited good stability in phosphate buffer saline (PBS). The micelles could release about 80% DOX in a quantitative fashion within 5 hours under a reductive environment. The intracellular drug release of DOX-loaded SS-PU-SS-PEG micelles increased upon incubation with Saos-2 cells in vitro. The micelles had good biocompatibility. In vitro, DOX-loaded SS-PU-SS-PEG micelles showed significant antitumor activity toward Saos-2 cells, which was close to that of free DOX. In vivo, DOX-loaded SS-PU-SS-PEG micelles exhibited better antitumor activity than free DOX. CONCLUSION: Findings from this study suggest that the SS-PU-SS-PEG micelles could achieve well-controlled tr...