Institute of Ultrasound Imaging & Department of Ultrasound, The Second Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ultrasound Molecular Imaging, Chongqing, 400010, PR China.
Institute of Ultrasound Imaging & Department of Ultrasound, The Second Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ultrasound Molecular Imaging, Chongqing, 400010, PR China; Department of Ultrasound, Maternal and Child Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430000, PR China.
Biomaterials. 2021 Apr;271:120710. doi: 10.1016/j.biomaterials.2021.120710. Epub 2021 Feb 9.
Fenton reaction-mediated chemodynamic therapy (CDT), which destroys tumor cells by converting HO into cytotoxic hydroxyl radical (OH) and singlet oxygen (O) species, is a promising field. However, Fenton-based CDT is severely impaired by the inappropriate tumor environment associated with undesirable intratumoral acidity and insufficient HO supply in tumor microenvironment (TME). Therefore, a strategy that can address these concerns is highly desired and beneficial for boosting such treatment. Herein, a magnetic nanoreactor system (denoted as poly (lactic-co-glycolic acid) (PLGA)-superparamagnetic iron oxide (SPIO)&vitamin C (Vc) was constructed with Vc in the core, SPIO on the shell, and PLGA as the building carrier. Upon low-intensity focused ultrasound irradiation, on-demand Vc release can locally decompose into HO, which can generate a favorable condition for facilitating SPIO-based Fenton-like reaction and result in continuous O and OH/O generation. The TME modulation-augmented CDT by this nanoreactor based on the reinforced Fenton reaction tremendously improved the antitumor outcomes, especially under increased accumulation contributed by magnetic targeting combined with enhanced permeability and retention effect. Moreover, the explosive production of oxygen can be monitored by real-time photoacoustic imaging, offering a noninvasive means to forecast the treatment efficacy. Therefore, this established microenvironment modulation strategy for augmenting Fenton reaction-based CDT paves a new avenue to realize highly efficient cancer theranostics.
芬顿反应介导的化学动力学治疗（CDT）通过将 HO 转化为细胞毒性羟基自由基（OH）和单线态氧（O）物种来破坏肿瘤细胞，是一个很有前途的领域。然而，基于芬顿的 CDT 受到与肿瘤微环境（TME）中不理想的肿瘤内酸度和 HO 供应不足相关的不合适肿瘤环境的严重影响。因此，需要一种能够解决这些问题的策略，这对于提高这种治疗方法非常有益。在此，构建了一种磁性纳米反应体系（记为聚（乳酸-共-乙醇酸）（PLGA）-超顺磁性氧化铁（SPIO）&维生素 C（Vc）），其中 Vc 为核，SPIO 为壳，PLGA 为构建载体。在低强度聚焦超声辐射下，按需释放 Vc 可以局部分解为 HO，这为促进基于 SPIO 的芬顿样反应并导致连续的 O 和 OH/O 生成创造了有利条件。这种基于强化芬顿反应的纳米反应体系增强的 TME 调制 CDT 极大地提高了抗肿瘤效果，尤其是在磁靶向作用增加和增强的渗透性和保留效应贡献下的积累增加。此外，氧气的爆炸产生可以通过实时光声成像进行监测，为预测治疗效果提供了一种非侵入性手段。因此，这种用于增强基于芬顿反应的 CDT 的微环境调节策略为实现高效的癌症治疗开辟了新途径。
