Department of Biomaterials, College of Materials, Research Center of Biomedical Engineering of Xiamen & Key Laboratory of Biomedical Engineering of Fujian Province & Fujian Provincial Key Laboratory for Soft Functional Materials Research, Xiamen University, Xiamen 361005, China.
State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry & Chemical Engineering, Xiamen University, Xiamen 361005, China.
Mol Pharm. 2020 Jul 6;17(7):2435-2450. doi: 10.1021/acs.molpharmaceut.0c00165. Epub 2020 Jun 5.
On-demand drug release nanoplatforms are promising alternative strategies for enhancing the therapeutic effect of cancer chemotherapy. However, these nanoplatforms still have many drawbacks including rapid blood clearance, nontargeted specificity, and a lack of immune escape function. Even worse, they are also hindered the dosage-limiting toxicity of traditional chemotherapeutic drugs. Herein, both dual-functional mannose (enhances the antitumor activity of chemotherapeutic drugs and exhibits an innate affinity against the lectin receptor) and amphiphilic d-α-tocopheryl polyethylene glycol 1000 succinate were selected to be covalently linked a redox-responsive monothioether linkage. The synthesized self-distinguished polymer (TSM), as a structural motif, can be self-assembled into nanoparticles (TSM NPs) in an aqueous solution, in which doxorubicin (DOX) is loaded by weak interactions (TSM-DOX NPs). These TSM-DOX NPs can provide targeted, on-demand drug release under dual stimuli from lysosomal acidity and glutathione (GSH). In addition, TSM-DOX NPs can be self-distinguished tumor cells and specifically self-distinguished from the tumor site . Further and research consistently demonstrated that TSM-DOX NPs display highly synergistic chemotherapeutic effects. Taken together, the data show that the self-distinguished GSH-responsive polymer TSM has the potential to load various therapeutic agents.
按需释放药物的纳米平台是增强癌症化疗疗效的有前途的替代策略。然而，这些纳米平台仍然存在许多缺点，包括快速血液清除、非靶向特异性和缺乏免疫逃逸功能。更糟糕的是，它们还受到传统化疗药物剂量限制毒性的阻碍。在此，选择双功能甘露糖（增强化疗药物的抗肿瘤活性，并对凝集素受体表现出固有亲和力）和两亲性 d-α-生育酚聚乙二醇 1000 琥珀酸通过还原响应性单硫醚键共价连接。合成的自区分聚合物（TSM）作为结构基元，可在水溶液中自组装成纳米颗粒（TSM NPs），其中阿霉素（DOX）通过弱相互作用（TSM-DOX NPs）负载。这些 TSM-DOX NPs 可以在溶酶体酸度和谷胱甘肽 (GSH) 的双重刺激下提供靶向、按需药物释放。此外，TSM-DOX NPs 可以自我区分肿瘤细胞并特异性地自我区分肿瘤部位。进一步的研究一致表明，TSM-DOX NPs 显示出高度协同的化疗效果。总之，数据表明，自区分的 GSH 响应性聚合物 TSM 有可能负载各种治疗剂。
