National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen, 518036, P. R. China.
Department of Bone & Joint Surgery, Peking University Shenzhen Hospital, Shenzhen, 518036, P. R. China.
J Mater Chem B. 2022 Jul 13;10(27):5263-5271. doi: 10.1039/d2tb00287f.
Sulfur dioxide (SO) based gas therapy has received great attention recently. Nevertheless, it is still a challenge to fabricate a SO delivery system to achieve effective delivery and on-demand stimuli triggered release at tumor sites. Herein, a chain-shattering polymeric SO prodrug micelle system was fabricated for effective SO based gas therapy. First, an amphiphilic polymer (mPEG-P(HDI-DN)) was prepared by polycondensation of poly(ethylene glycol) methyl ether, hexamethylene diisocyanate and monomer containing SO. mPEG-P(HDI-DN) can self-assemble into spherical micelles with a diameter of around 50-90 nm. Triggered release of SO from micelles can be achieved in the presence of GSH with the degradation of mPEG-P(HDI-DN) into small molecules. The experiment proved that mPEG-P(HDI-DN) micelles can enter into osteosarcoma cells and inhibit the growth of osteosarcoma cells by increasing the ROS level in cells. The experiments demonstrate that mPEG-P(HDI-DN) micelles can inhibit the growth of osteosarcoma effectively without obvious tissue toxicity. These results indicate that this chain-shattering polymeric SO prodrug micelle system is a promising candidate for effective SO based gas therapy.
二氧化硫（SO）气体治疗最近受到了广泛关注。然而，仍然存在挑战，需要开发一种 SO 递送系统，以在肿瘤部位实现有效的递送和按需刺激触发释放。在此，我们构建了一种链断裂聚合物 SO 前药胶束系统，用于有效的 SO 气体治疗。首先，通过聚乙二醇甲醚、六亚甲基二异氰酸酯和含有 SO 的单体的缩聚反应制备了一种两亲性聚合物（mPEG-P（HDI-DN））。mPEG-P（HDI-DN）可以自组装成直径约 50-90nm 的球形胶束。在 GSH 的存在下，通过 mPEG-P（HDI-DN）的降解可以实现 SO 的触发释放。实验证明 mPEG-P（HDI-DN）胶束可以进入骨肉瘤细胞，并通过增加细胞内的 ROS 水平抑制骨肉瘤细胞的生长。实验表明 mPEG-P（HDI-DN）胶束可以有效抑制骨肉瘤的生长，而没有明显的组织毒性。这些结果表明，这种链断裂聚合物 SO 前药胶束系统是一种很有前途的有效 SO 气体治疗候选物。
