BACKGROUND Developing new strategies to reduce the output power of microwave (MW) ablation while keeping anti-tumor effect are highly desirable for the simultaneous achievement of effective tumor killing and avoidance of complications. We find that mild MW irradiation can significantly increase intracellular Ca2+ concentration in the presence of doxorubicin hydrochloride (DOX) and thus induce massive tumor cell apoptosis. Herein, we designed a synergistic nanoplatform that not only amplifies the intracellular Ca2+ concentration and induce cell death under mild MW irradiation but also avoids the side effect of thermal ablation and chemotherapy. RESULTS The as-made NaCl-DOX@PLGA nanoplatform selectively elevates the temperature of tumor tissue distributed with nanoparticles under low-output MW, which further prompts the release of DOX from the PLGA nanoparticles and tumor cellular uptake of DOX. More importantly, its synergistic effect not only combines thermal ablation and chemotherapy, but also obviously increases the intracellular Ca2+ concentration. Changes of Ca2+ broke the homeostasis of tumor cells, decreased the mitochondrial inner membrane potential and finally induced the cascade of apoptosis under nonlethal temperature. As such, the NaCl-DOX@PLGA efficiently suppressed the tumor cell progression in vivo and in vitro under mild MW irradiation for the triple synergic effect. CONCLUSIONS This work provides a biocompatible and biodegradable nanoplatform with triple functions to realize the effective tumor killing in unlethal temperature. Those findings provide reliable solution to solve the bottleneck problem bothering clinics about the balance of thermal efficiency and normal tissue protection.

中文翻译：

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放大的细胞内Ca2 +用于微波消融和化疗的协同抗肿瘤治疗。

背景技术为了同时实现有效的肿瘤杀死和避免并发症，迫切需要开发新的策略来降低微波消融的输出功率，同时保持抗肿瘤效果。我们发现轻度的MW辐射可以在存在盐酸阿霉素（DOX）的情况下显着增加细胞内Ca2 +的浓度，从而诱导大量肿瘤细胞凋亡。本文中，我们设计了一种协同纳米平台，该平台不仅可以放大细胞内Ca2 +的浓度并在轻度MW辐射下诱导细胞死亡，而且还避免了热消融和化学疗法的副作用。结果制成的NaCl-DOX @ PLGA纳米平台在低输出MW下选择性升高了分布有纳米颗粒的肿瘤组织的温度，这进一步促进了DOGA从PLGA纳米颗粒中的释放以及肿瘤细胞对DOX的吸收。更重要的是，它的协同作用不仅结合了热消融和化学疗法，而且还明显增加了细胞内Ca2 +的浓度。Ca 2+的变化破坏了肿瘤细胞的稳态，降低了线粒体内膜的电位，并最终在非致死温度下诱导了细胞凋亡的级联反应。这样，NaCl-DOX @ PLGA在轻度MW辐射下可有效抑制体内和体外肿瘤细胞的进展，从而发挥三重协同作用。结论这项工作提供了具有三重功能的生物相容性和可生物降解的纳米平台，以实现在非致死温度下的有效肿瘤杀死。