Self-Assembled Acid-Responsive Nanosystem for Synergistic Anti-Angiogenic/Photothermal/Ferroptosis Therapy against Esophageal Cancer
Self-Assembled Acid-Responsive Nanosystem for Synergistic Anti-Angiogenic/Photothermal/Ferroptosis Therapy against Esophageal Cancer
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DOI：
10.1002/adhm.202302787
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发表时间：
2023-11-28
影响因子：
10
通讯作者：
Yuan，Yong
中科院分区：
文献类型：
--
作者：
Li，Xiaokun;Li，Jiamei;Yuan，Yong
由于抗血管生成剂的非细胞毒性和非特异性生物分布，通过抗血管生成疗法治疗食管癌（EC）面临挑战。因此，寻求一种协同治疗模式和一种有效解决EC的靶向递送方法已变得势在必行。在这项研究中，设计了一种酸响应性释放纳米系统（Bev‐IR820@FeIIITA），该系统涉及贝伐单抗（一种抗血管生成的单克隆抗体）与TA和Fe 3+结合形成金属酚醛网络，然后负载近红外光热剂（IR 820）以实现联合治疗。Bev‐IR820@FeIIITA的构建可以通过简单的自组装过程实现。Bev‐IR820@FeIIITA具有肿瘤靶向能力和协同治疗作用，包括抗血管生成治疗、光热治疗（PTT）和铁凋亡治疗（FT）。Bev‐IR820@FeIIITA通过其pH响应性释放特性在将药物递送至EC组织方面表现出卓越的能力。因此，贝伐单抗通过阻断肿瘤血管生成发挥其治疗作用，从而阻碍肿瘤生长。同时，PTT促进肿瘤部位的局部热消融，直接根除EC细胞。FT与PTT协同作用，引起活性氧（ROS）风暴的形成，随后最终导致EC细胞的死亡。总之，这种合并治疗方式具有协同阻止EC进展的实质性希望，并展示了未来EC治疗的良好前景。
Esophageal cancer (EC) treatment via anti‐angiogenic therapy faces challenges due to non‐cytotoxicity and non‐specific biodistribution of the anti‐angiogenic agents. Hence, the quest for a synergistic treatment modality and a targeted delivery approach to effectively address EC has become imperative. In this study, an acid‐responsive release nanosystem (Bev‐IR820@FeIIITA) that involves the conjugation of bevacizumab, an anti‐angiogenic monoclonal antibody, with TA and Fe3+to form a metal‐phenolic network, followed by loading with the near‐infrared photothermal agent (IR820) to achieve combinational therapy, is designed. The construction of Bev‐IR820@FeIIITA can be realized through a facile self‐assembly process. The Bev‐IR820@FeIIITA exhibits tumor‐targeting capabilities and synergistic therapeutic effects, encompassing anti‐angiogenic therapy, photothermal therapy (PTT), and ferroptosis therapy (FT). Bev‐IR820@FeIIITA exhibits remarkable proficiency in delivering drugs to EC tissue through its pH‐responsive release properties. Consequently, bevacizumab exerts its therapeutic effects by obstructing tumor angiogenesis, thereby impeding tumor growth. Meanwhile, PTT facilitates localized thermal ablation at the tumor site, directly eradicating EC cells. FT synergistically collaborates with PTT, giving rise to the formation of a reactive oxygen species (ROS) storm, subsequently culminating in the demise of EC cells. In summary, this amalgamated treatment modality carries substantial promise for synergistically impeding EC progression and showcases auspicious prospects for future EC treatment.