Wang Junrui, Song Weixiang, Wang Xingyue, Xie Zhuoyan, Zhang Wenli, Jiang Weixi, Liu Shuling, Hou Jingxin, Zhong Yixin, Xu Jie, Ran Haitao, Guo Dajing
Department of Radiology, Second Affiliated Hospital of Chongqing Medical University, No. 74 Linjiang Rd, Yuzhong District, Chongqing, 400010, PR China; Chongqing Key Laboratory of Ultrasound Molecular Imaging & Department of Ultrasound, Second Affiliated Hospital of Chongqing Medical University, No. 74 Linjiang Rd, Yuzhong District, Chongqing, 400010, PR China.
Department of Radiology, Second Affiliated Hospital of Chongqing Medical University, No. 74 Linjiang Rd, Yuzhong District, Chongqing, 400010, PR China.
Biomaterials. 2021 Oct;277:121100. doi: 10.1016/j.biomaterials.2021.121100. Epub 2021 Sep 2.
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.
基于铁死亡的纳米药物由于这种非传统凋亡模式的优势，在抗肿瘤治疗中受到越来越多的关注，但药物递送至肿瘤部位的困难以及到达后从表面到核心的穿透问题严重阻碍了其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策略，即注射磁性纳米液滴（MNDs）来解决这两个长期存在的问题。MNDs是一种可以携带多功能药物和成像材料的纳米载体。MNDs可以通过主动肿瘤靶向（多功能药物）和被动肿瘤靶向（增强渗透和滞留效应）有效地在肿瘤部位积累，在多模态成像引导下，通过温和温度的磁流体热疗（MHT）使MNDs从表面扩散到核心。最后，通过药物释放激活肿瘤部位深处的铁死亡途径。这种方法的灵感来源于温和温度的MHT能够使MNDs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，从而放大铁死亡的抗肿瘤疗效。这种策略被称为“热铁死亡增敏”。重要的是，这种行为可以在多模态成像的引导下进行，使得用于癌症治疗的MNDs设计更加安全和合理。
