MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, South China Normal University, Guangzhou, 510631, China.
Nanoscale. 2019 Jan 23;11(4):1710-1719. doi: 10.1039/c8nr08498j.
Microwave irradiation is a powerful non-invasive approach for treating deep-seated diseases in a clinical setting. Pulsed microwave-induced thermoacoustic cavitation allows precise cancer treatment with microwave-absorbing materials. This differs from the traditional continuous microwave-induced thermotherapy which may be harmful to off-target tissues. Here we first report the integration of thermocavitation and cytoplasmic drug release into highly explosible cell-penetrating nanocapsules for effective tumor inhibition under pulsed microwave irradiation. The nanocapsules were formulated from arginine-tethered reduction-responsive copolymers, P(ArgMA-co-DMA)-b-PPOPMA, microwave-absorbing AB and chemotherapeutic DOX using a double-emulsion method. The nanocapsules were internalized by cancer cells rapidly via major energy-independent pathways. Upon pulsed microwave irradiation, AB absorbed energy to generate a giant thermoacoustic shockwave, simultaneously decomposing into carbon dioxide and ammonia which enforced the cavitation damage effect. The thermoacoustic shockwave and gas burst also mechanically disrupted the intracellular organelles resulting in high-ratio cell necrosis and promoted the cytosolic release of DOX into the nucleus to initiate cell death. Importantly, in vivo results demonstrated significantly suppressed tumor growth by the pulsed microwave-triggered thermocavitation and drug release, and minimal systemic toxicity from the microwave treatment. Therefore, our study provides a new strategy for effectively engineering pulsed microwave-responsive nanomaterials for smart cancer therapy.
微波辐射是一种强大的非侵入性方法，可用于临床治疗深部疾病。脉冲微波诱导热声空化允许使用微波吸收材料进行精确的癌症治疗。这与传统的连续微波诱导热疗不同，后者可能对非目标组织有害。在这里，我们首次报道了将热空化和细胞质药物释放集成到高爆炸细胞穿透纳米胶囊中，以便在脉冲微波辐射下有效抑制肿瘤。纳米胶囊由精氨酸连接的还原响应性共聚物 P(ArgMA-co-DMA)-b-PPOPMA、微波吸收 AB 和化疗药物 DOX 采用双乳液法制备而成。纳米胶囊通过主要非能量依赖途径被癌细胞快速内化。在脉冲微波辐射下，AB 吸收能量产生巨大的热声冲击波，同时分解成二氧化碳和氨，增强空化损伤效应。热声冲击波和气体爆发也会机械破坏细胞内细胞器，导致高比例的细胞坏死，并促进 DOX 向核内的细胞质释放，从而引发细胞死亡。重要的是，体内结果表明，脉冲微波触发的热空化和药物释放显著抑制了肿瘤生长，并且微波治疗的全身毒性最小。因此，我们的研究为有效地工程化脉冲微波响应纳米材料用于智能癌症治疗提供了一种新策略。
