School of Materials Science and Engineering, Key Laboratory of Advanced Civil Materials of Ministry of Education, Tongji University, Shanghai 201804, P. R. China.
J Mater Chem B. 2023 Apr 26;11(16):3727-3739. doi: 10.1039/d3tb00248a.
Efficient synergistic therapeutic strategies for tumors with high specificity and sensitivity remain a major challenge. An injectable near-infrared (NIR)-responsive supramolecular hydrogel was prepared host-guest interactions between conjugated poly(-phenylglycine)-poly(ethylene glycol) (PNPG-PEG) and α-cyclodextrin. A reactive oxygen species (ROS)-triggered chain-breakage prodrug was composed of a thioketal (TK) linkage of methoxy poly(ethylene glycol) (mPEG) and doxorubicin (DOX). The resulting amphiphilic conjugate mPEG-TK-DOX can self-assemble into prodrug micelles. PEG/poly(etherimide) (PEI)@FeO nanoparticles (PEG/PEI@FeO NPs) were prepared using a thermal decomposition method. The prodrug micelles and PEG/PEI@FeO NPs can be well dispersed into the hydrogel system. In a tumor micro-acid environment, PEG/PEI@FeO NPs catalyze the decomposition of HO to highly toxic ˙OH a Fenton reaction to induce the breakage of ROS-responsive TK bonds for the dissociation of micelles and the continuous release of DOX. PEG/PEI@FeO NPs can also generate an NIR-thermal effect and enhance the photothermal therapy. Notably, by combining with controllable photothermal therapy, the composite hydrogel system shows enhanced synergistic chemo-photothermal therapy for tumors and almost complete and tumor suppression, providing a promising synergistic tumor treatment strategy.
高效协同的肿瘤治疗策略需要高特异性和灵敏度，这仍然是一个主要的挑战。本研究通过主体-客体相互作用，制备了一种可注射的近红外（NIR）响应超分子水凝胶。该水凝胶由共轭聚（对苯甘氨酸）-聚乙二醇（PNPG-PEG）和α-环糊精组成。一种活性氧（ROS）触发的链断裂前药由甲氧基聚乙二醇（mPEG）和阿霉素（DOX）的硫缩酮（TK）连接组成。所得两亲性共轭物 mPEG-TK-DOX 可以自组装成前药胶束。采用热分解法制备了 PEG/聚醚酰亚胺（PEI）@FeO 纳米粒子（PEG/PEI@FeO NPs）。前药胶束和 PEG/PEI@FeO NPs 可以很好地分散在水凝胶体系中。在肿瘤微酸性环境中，PEG/PEI@FeO NPs 可以催化 HO 的分解产生高毒性的˙OH，同时发生芬顿反应，导致 ROS 响应性 TK 键的断裂，从而实现胶束的解离和 DOX 的持续释放。PEG/PEI@FeO NPs 还可以产生 NIR 热效应，增强光热治疗效果。值得注意的是，通过与可控光热治疗相结合，该复合水凝胶系统表现出增强的协同化学-光热肿瘤治疗效果，几乎完全抑制了肿瘤的生长和转移，为协同肿瘤治疗提供了一种有前景的策略。
