Tumor-self-targeted "thermoferroptosis-sensitization" magnetic nanodroplets for multimodal imaging-guided tumor-specific therapy
Tumor-self-targeted "thermoferroptosis-sensitization" magnetic nanodroplets for multimodal imaging-guided tumor-specific therapy
复制标题
肿瘤自靶向“热铁死亡敏化”磁性纳米液滴用于多模态成像引导的肿瘤特异性治疗
DOI：
10.1016/j.biomaterials.2021.121100
复制
发表时间：
2021
期刊：
影响因子：
14
通讯作者：
Guo Dajing
中科院分区：
文献类型：
--
作者：
Wang Junrui;Song Weixiang;Wang Xingyue;Xie Zhuoyan;Zhang Wenli;Jiang Weixi;Liu Shuling;Hou Jingxin;Zhong Yixin;Xu Jie;Ran Haitao;Guo Dajing
基于铁凋亡的纳米药物由于这种非常规的凋亡模式的优点而在抗肿瘤治疗中越来越受到关注，但递送到肿瘤部位和到达后的表面到核心渗透的困难严重阻碍了进一步的临床转化和应用。在此，我们提出了一种前所未有的注入磁性纳米液滴（MND）的策略来解决这两个长期存在的问题。MND是一种纳米载体，可以携带多功能药物和成像材料。通过主动肿瘤靶向（多功能药物）和被动肿瘤靶向（增强的渗透性和保留效应），MND可以有效地在肿瘤部位积聚，允许MND通过多模态成像引导下的中温磁流体热疗（MHT）从表面扩散到核心。最后，通过药物释放，铁凋亡途径在肿瘤部位深处被激活。这种方法的灵感来自于中温MHT允许MND快速穿过血管-肿瘤屏障并从表面到核心深入穿透肿瘤组织以放大铁凋亡的抗肿瘤功效的能力。这种策略被称为“热铁性凋亡致敏”。重要的是，这种行为可以在多模态成像的指导下进行，使得用于癌症治疗的MND的设计更安全，更合理。
Ferroptosis-based nanomedicine has drawn increasing attention in antitumor therapy because of the advantages of this unconventional mode of apoptosis, but the difficulties of delivery to the tumor site and surface-to-core penetration after arrival seriously hinder further clinical transformation and application. Herein, we propose an unprecedented strategy of injecting magnetic nanodroplets (MNDs) to solve these two longstanding problems. MNDs are nanocarriers that can carry multifunctional drugs and imaging materials. MNDs can effectively accumulate in the tumor site by active tumor targeting (multifunctional drugs) and passive tumor targeting (enhanced permeability and retention effect), allowing diffusion of the MNDs from the surface to the core through mild-temperature magnetic fluid hyperthermia (MHT) under multimodal imaging guidance. Finally, the ferroptosis pathway is activated deep within the tumor site through the drug release. This approach was inspired by the ability of mild-temperature MHT to allow MNDs to quickly pass through the blood vessel-tumor barrier and deeply penetrate the tumor tissue from the surface to the core to amplify the antitumor efficacy of ferroptosis. This strategy is termed as “thermoferroptosis sensitization”. Importantly, this behavior can be performed under the guidance of multimodal imaging, making the design of MNDs for cancer therapy safer and more reasonable.