State Key Laboratory of Silkworm Genome Biology, School of Materials and Energy, Southwest University, Chongqing 400715, China.
Department of Nuclear Medicine, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, China.
ACS Nano. 2021 Jul 27;15(7):11953-11969. doi: 10.1021/acsnano.1c03128. Epub 2021 Jun 18.
A hypoxic and acidic tumor microenvironment (TME) plays a significant role in cancer development through complex cellular signaling networks, and it is thus challenging to completely eradicate tumors monotherapy. Here, PEGylated CoFeO nanoflowers (CFP) with multiple enzymatic activities, serving as bioreactors responsive to TME cues, were synthesized a typical solvothermal method for augmented sonodynamic therapy (SDT) and chemodynamic therapy (CDT) with elicitation of robust immune response. The CFP occupying multivalent elements (Co, Fe) exhibited strong Fenton-like and catalase-like activity. In another aspect, CFP itself is a brand-new sonosensitizer for high-performance SDT based on ultrasound-triggered electron (e)/hole (h) pair separation from the energy band with promptness and high efficiency. With efficient enrichment in tumorous tissue as revealed by magnetic resonance imaging, CPF could generate OH for CDT relying on Fenton-like reactions. Moreover, catalase-mimicking CFP could react with endogenous HO to generate molecular oxygen, and high O level may promote the production of O for SDT. What's more, the reactive oxygen species obtained from combined SDT/CDT could efficiently trigger immunogenic cell death through a synergistic therapy based on the elicitation of antitumor immunity with the aid of an immune checkpoint blockade for the sake of suppressing primary and distant tumors as well as lung metastasis. Taken together, this paradigm delivers useful insights for developing in-coming nanocomposites based on cobalt ferrite for cancer theranostics.
缺氧和酸性的肿瘤微环境（TME）通过复杂的细胞信号网络在癌症发展中起着重要作用，因此单靠药物治疗很难完全根除肿瘤。在这里，通过典型的溶剂热法合成了具有多种酶活性的聚乙二醇化 CoFeO 纳米花（CFP），作为对 TME 信号响应的生物反应器，用于增强声动力治疗（SDT）和化学动力治疗（CDT），并引发强烈的免疫反应。CFP 占据多价元素（Co、Fe），表现出强烈的类芬顿和过氧化氢酶样活性。另一方面，CFP 本身是一种全新的超声敏化剂，可基于超声触发的能带内电子（e）/空穴（h）对分离实现高效 SDT。通过磁共振成像显示，CFP 可以在肿瘤组织中高效富集，并通过类芬顿反应产生 CDT 所需的 OH。此外，模仿过氧化氢酶的 CFP 可以与内源性 HO 反应生成分子氧，而高 O 水平可能促进 SDT 中 O 的产生。更重要的是，联合 SDT/CDT 产生的活性氧可以通过免疫检查点阻断辅助的抗肿瘤免疫来有效地引发免疫原性细胞死亡，从而抑制原发和远处肿瘤以及肺转移。总之，该范例为开发基于钴铁氧体的新型纳米复合材料用于癌症治疗提供了有用的见解。
