Hollow magnetic nanosystem-boosting synergistic effect between magnetic hyperthermia and sonodynamic therapy via modulating reactive oxygen species and heat shock proteins
Hollow magnetic nanosystem-boosting synergistic effect between magnetic hyperthermia and sonodynamic therapy via modulating reactive oxygen species and heat shock proteins
复制标题
空心磁性纳米系统通过调节活性氧和热休克蛋白增强磁热疗和声动力疗法之间的协同效应
DOI：
10.1016/j.cej.2020.124521
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发表时间：
2020
影响因子：
15.1
通讯作者：
Lin Xianfang
中科院分区：
文献类型：
--
作者：
Zhang Yang;Xu Yanjun;Sun Di;Meng Zheying;Ying Weiwei;Gao Wei;Hou Rui;Zheng Yuanyi;Cai Xiaojun;Hu Bing;Lin Xianfang
交变磁场（AMF）触发的磁热疗（MHT）作为一种具有空间和时间控制的治疗模式，在克服传统局部治疗的缺点方面具有广阔的应用前景。然而，在热休克蛋白（HSPs）的存在下，MHT的功效仍然不令人满意。此外，持续的肿瘤缺氧困扰着实体瘤治疗的实际意义。本文设计并合成了一种由空心氧化铁纳米粒子（HIONs）、Fe3O4和声敏剂血卟啉（HP）组成的新型磁性纳米体系。中空的HION显示出用于装载声敏剂分子的大内腔，并且具有纳米酶活性，用于催化内源性过氧化氢（H2O2）的分解以产生可以克服肿瘤缺氧的分子氧（O2），从而增强声动力学疗法（SDT）诱导的高毒性活性氧（ROS）的产生，用于有效的癌细胞凋亡。重要的是，产生的ROS还可以激活HSP的切割，从而进一步消除热耐受性并促进MHT功效。协同催化增强的SDT效率和MHT效应实现了最有效的肿瘤抑制功效。本工作为多功能策略开发了一种通用的纳米平台，并通过合理设计其结构来拓宽其生物应用。
As a promising treatment modality with spatial and temporal control, alternating magnetic field (AMF) triggered magnetic hyperthermal therapy (MHT) shows broad and promising applications to overcome the drawbacks of traditional focal therapies in combating cancer. However, the MHT efficacy is still not satisfactory with the presence of heat shock proteins (HSPs). In addition, sustained tumor hypoxia haunts practical implications for the treatment of solid tumors. Herein, a novel magnetic nanosystem composed of hollow iron oxide nanoparticles (HIONs), Fe3O4, and sonosensitizers, hematoporphyrin (HP) was rationally designed and successfully synthesized. The hollow HIONs show a large inner cavity for loading sonosensitizer molecules and possess nanozyme activity for catalyzing decomposition of endogenous overexpressed hydrogen peroxide (H2O2) to produce molecular oxygen (O2) that can overcome tumor hypoxia, thus augmenting the sonodynamic therapy (SDT)-induced highly toxic reactive oxygen species (ROS) production for efficient cancer cell apoptosis. Importantly, the generated ROS can also activates the cleavage of HSPs that further eliminate themotolerance and facilitates MHT efficacy. The synergistic catalysis-enhanced SDT efficiency and MHT effect realized most potent tumor suppression efficacy. This work develops a versatile nanoplatform for a multifunctional strategy and broadens the biological applications by rationally designing their structure.