Photosynthetic Oxygenation-Augmented Sonodynamic Nanotherapy of Hypoxic Tumors
Photosynthetic Oxygenation-Augmented Sonodynamic Nanotherapy of Hypoxic Tumors
复制标题
缺氧肿瘤的光合氧化增强声动力纳米疗法
DOI：
10.1002/adhm.202102135
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发表时间：
2021
影响因子：
10
通讯作者：
Zhongqian Hu
中科院分区：
文献类型：
--
作者：
Shuting Lu;Wei Feng;Caihong Dong;Xinran Song;Xiang Gao;Jinhe Guo;Yu Chen;Zhongqian Hu
活性氧（Reactive oxygen species，ROS）是一种通过氧化应激而抑制肿瘤生长的有效药物。作为一种新兴的ROS参与的非侵入性抗癌治疗方式，声动力学治疗（SDT）具有高组织穿透深度和良性远程时空选择性，已逐渐被用作基于ROS的肿瘤治疗的独特替代方案。然而，缺氧的肿瘤微环境实质上限制了声动力学效应。在这项工作中，基于光合微生物蓝细菌（Cyan）与超小型缺氧氧化物Mn1.4WOx纳米声致敏剂（称为M@C）的氧自给混合声致敏剂被设计和工程化，以克服缺氧诱导的肿瘤抗性的关键问题并加强SDT效应。Cyan在光照下持续的光合氧产生可以促进Mn1.4WOx纳米增敏剂在体外和体内超声（US）照射下产生更多的ROS对抗癌细胞。特别是，用于抑制缺氧诱导因子1 α（HIF-1α）基因表达的持续氧气释放进一步增强和提高了SDT效率。因此，这项工作提供了一个范例，即合理工程化的基于生物杂交微生物的多功能声敏剂可以作为一个有效的生物平台，用于提高SDT的治疗效率，特别是用于治疗缺氧肿瘤。
Reactive oxygen species (ROS) has been employed as a powerful therapeutic agent for eradicating tumor via oxidative stress. As an emerging ROS‐involving noninvasive anticancer therapeutic modality, sonodynamic therapy (SDT) with high tissue penetration depth and benign remote spatiotemporal selectivity has been progressively utilized as the distinct alternative for ROS‐based tumor treatment. However, the hypoxic tumor microenvironment substantially restricts the sonodynamic effect. In this work, an oxygen self‐sufficient hybrid sonosensitizer on the basis of photosynthetic microorganisms cyanobacteria (Cyan) integrated with ultrasmall oxygen‐deficient bimetallic oxide Mn1.4WOxnanosonosensitizers, termed as M@C, is designed and engineered to overcome the critical issue of hypoxia‐induced tumor resistance and strengthen the SDT effect. The sustained photosynthetic oxygen production by Cyan under light illumination can promote Mn1.4WOxnanosonosensitizers to produce more ROS against cancer cells both in vitro and in vivo under ultrasound (US) irradiation. Especially, the sustained oxygen evolution for suppressing the gene expression of hypoxia‐inducible factor 1alpha (HIF‐1α) further boosts and augments the SDT efficiency. Thus, this work provides the paradigm that the rationally engineered biohybrid microorganism‐based multifunctional sonosensitizers can serve as an effective bioplatform for augmenting the therapeutic efficiency of SDT, particularly for the treatment of hypoxic tumors.