Abstract：
The implementation of chemoradiation combinations has gained great momentum in clinical practices. However, the full utility of this paradigm is often restricted by the discordant tempos of action of chemotherapy and radiotherapy. Here, a gold nanoparticle-based radiation-responsive nanovesicle system loaded with cisplatin and veliparib, denoted as CV-Au NVs, is developed to augment the concurrent chemoradiation effect in a spatiotemporally controllable manner of drug release. Upon irradiation, the in situ generation of •OH induces the oxidation of polyphenylene sulfide from being hydrophobic to hydrophilic, resulting in the disintegration of the nanovesicles and the rapid release of the entrapped cisplatin and veliparib (the poly ADP-ribose polymerase (PARP) inhibitor). Cisplatin-induced DNA damage and the impairment of the DNA repair mechanism mediated by veliparib synergistically elicit potent pro-apoptotic effects. In vivo studies suggest that one-dose injection of the CV-Au NVs and one-time X-ray irradiation paradigm effectively inhibit tumor growth in the A549 lung cancer model. This study provides new insight into designing nanomedicine platforms in chemoradiation therapy from a vantage point of synergizing both chemotherapy and radiation therapy in a spatiotemporally concurrent manner.
摘要：
放化疗组合的实施在临床实践中获得了巨大的势头。然而,这种模式的全部效用通常受到化疗和放疗不一致的作用节奏的限制。这里,我们开发了一种基于金纳米粒子的辐射响应纳米囊泡系统，负载顺铂和维利帕里布，表示为CV-AuNVs，以时空可控的药物释放方式增强同步放化效应。照射后，•OH的原位生成诱导聚苯硫醚从疏水到亲水的氧化，导致纳米囊泡的崩解和包埋的顺铂和Veliparib（PARP抑制剂）的快速释放。顺铂诱导的DNA损伤和维利帕尼介导的DNA修复机制受损协同引发了有效的促凋亡作用。体内研究表明，在A549肺癌模型中，一次剂量注射CV-AuNVs和一次X射线照射范式可有效抑制肿瘤生长。这项研究提供了新的见解，从协同协同化疗和放射治疗在时空方式放化疗治疗中设计纳米医学平台。本文受版权保护。保留所有权利。
