As one of the most promising drug-delivery carriers due to its small size, easy surface modifiability, and hydrophobic interior, cationic poly(amidoamine) (PAMAM) per se, demonstrated by previous reports and the authors’ present study, indicate potential anticancer capability, however, which are restricted by autophagy elicitation. Besides, its side-toxicity profile, having also been extensively documented, limits its translation into the clinic. Herein, the authors design a photoresponsive PAMAM-assembled nanoparticle loaded with the autophagy inhibitor (chloroquine, CQ), which exhibits light responsiveness for precisely controlling drug release and superior dark biosafety. Upon light irradiation, the nanoparticle can dissociate into charged small PAMAM for a significant antitumor effect. Meanwhile, the released CQ can inhibit pro-survival autophagy induced by PAMAM to achieve an excellent synergistic anticancer efficacy in vitro and in vivo. The authors’ study provided a vision of utilizing PAMAM as self-carried anticancer therapeutics in combination with an autophagy inhibitor and proposing a cancer therapy with high antitumor efficacy and low side effects to normal tissues.

中文翻译：

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载有自噬抑制剂的光响应 PAMAM 组装纳米载体用于协同癌症治疗

作为最有前途的药物输送载体之一，由于其体积小、易于表面改性和内部疏水，阳离子聚（酰胺胺）（PAMAM）本身，如先前的报告和作者的本研究所示，表明具有潜在的抗癌能力然而，它们受到自噬诱导的限制。此外，它的副作用也被广泛记录，限制了它在临床上的应用。在此，作者设计了一种负载自噬抑制剂（氯喹，CQ）的光响应 PAMAM 组装纳米颗粒，该纳米颗粒具有光响应性，可精确控制药物释放并具有卓越的暗生物安全性。在光照射下，纳米颗粒可以分解成带电的小 PAMAM，具有显着的抗肿瘤作用。同时，释放的CQ可以抑制PAMAM诱导的促生存自噬，从而在体外和体内实现优异的协同抗癌功效。作者的研究提供了一个愿景，即利用 PAMAM 作为自体抗癌疗法与自噬抑制剂相结合，并提出了一种具有高抗肿瘤功效和对正常组织副作用低的癌症疗法。