Currently single photosensitizers or chemotherapeutics implemented in clinic present huge challenges in terms of non-selective toxicity, physiological instability and unfavorable therapeutic efficacy. Herein, we designed a versatile polycondensate-based strategy for the preparation of redox-responsive prodrug nanogels (NGs) for enhanced synergistic cancer therapy. Concretely, based on a reductive cross-linking of purpurin 18 (P18) and 10-hydroxycamplothecin (HCPT), a well-designed prodrug nanogel (denoted as DPH NGs) with suitable size (∼67 nm) was fabricated, which exhibited high drug loading, controlled drug release and deepened tumor penetration. The high concentration of glutathione (GSH) in the tumor microenvironment (TME) is capable of being consumed by dense disulfide bonds in DPH NGs, promoting the generation of reactive oxygen species (ROS) after irradiation at 660 nm, thus reshape the TME to reinforce photodynamic therapy against malignancies. In addition, P18 can be served as a powerful NIR fluorescence (NIRF)/ magnetic resonance (MR) imaging ability. Pleasantly, DPH NGs showed amplified oxidative stress in tumor cells to achieve an enhanced chemo-photodynamic therapy with the real-time MR/NIRF dual-modal imaging. Our findings in this study may blow up a storm for devising a simple and versatile strategies for multi-drug delivery and combined cancer therapy.

当前在临床上实施的单一光敏剂或化学治疗剂在非选择性毒性，生理不稳定和不利的治疗功效方面提出了巨大的挑战。在这里，我们设计了一种基于多缩聚物的通用策略，用于制备氧化还原反应性前药纳米凝胶（NGs），以增强协同癌症治疗的作用。具体而言，基于紫嘌呤18（P18）和10-羟基喜树碱（HCPT）的还原性交联，制得了设计合理，尺寸合适（〜67 nm）的前药纳米凝胶（表示DPH NGs），并显示出高药效。载量，控制药物释放，加深肿瘤的渗透。肿瘤微环境（TME）中的高浓度谷胱甘肽（GSH）能够被DPH NG中的致密二硫键所消耗，促进在660 nm照射后产生活性氧（ROS），从而重塑TME以增强针对恶性肿瘤的光动力疗法。此外，P18可以用作强大的NIR荧光（NIRF）/磁共振（MR）成像功能。令人高兴的是，DPH NGs通过实时MR / NIRF双模态成像显示了肿瘤细胞中放大的氧化应激，从而实现了增强的化学光动力疗法。我们在这项研究中的发现可能会激起一场风暴，该浪潮为多药输送和癌症联合治疗设计一种简单而通用的策略。DPH NGs通过实时MR / NIRF双模态成像显示出肿瘤细胞中的氧化应激放大，从而实现了增强的化学光动力疗法。我们在这项研究中的发现可能会激起一场风暴，该浪潮为多药输送和癌症联合治疗设计一种简单而通用的策略。DPH NGs通过实时MR / NIRF双模态成像显示出肿瘤细胞中的氧化应激放大，从而实现了增强的化学光动力疗法。我们在这项研究中的发现可能会激起一场风暴，该浪潮为多药输送和癌症联合治疗设计一种简单而通用的策略。