Design of novel theranostic nanoplatforms integrating precision dynamic imaging modalities, tumor targeting ligands and therapeutic components with enhanced tumor accumulation still remains to be challenging. Here we report a facile strategy to prepare cell membrane (CM)-coated nanoclusters assembled from ultrasmall iron oxide nanoparticles (USIO NPs) with pH-responsiveness as a nanocarrier to load anti-cancer drug doxorubicin (DOX). Citric-stabilized USIO NPs with a size of 3.2 nm were synthesized, modified to have surface amine groups, and crosslinked to obtain pH-responsive nanoclusters (NCs). Then, the formed USIO NCs were loaded with DOX, and coated with cancer CMs to render them with resistance to macrophage cellular uptake and homologous cancer cell targeting specificity. Within the acidic tumor microenvironment, the pH-responsive USIO NCs/DOX@CM with dominant T magnetic resonance (MR) imaging performance can be dissociated to form single USIO NPs with T MR imaging ability, and simultaneously rapidly release DOX, thereby enabling dynamic T/T-weighted MR imaging and chemotherapy of tumors. Further, through the ultrasound-induced sonoporation effect, the dynamic MR imaging and tumor chemotherapy can be further enhanced. The designed USIO NCs/DOX@CM may be developed as a versatile theranostic platform for ultrasound-enhanced targeted precision theranostics of different cancer types.

中文翻译：

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使用由超小型氧化铁纳米粒子组装而成的细胞膜涂层和 pH 响应纳米簇进行超声增强精准肿瘤治疗诊断

整合精确动态成像模式、肿瘤靶向配体和增强肿瘤积累的治疗成分的新型治疗诊断纳米平台的设计仍然具有挑战性。在这里，我们报告了一种简便的策略，制备由具有 pH 响应性的超小氧化铁纳米颗粒 (USIO NP) 组装而成的细胞膜 (CM) 涂层纳米簇，作为负载抗癌药物阿霉素 (DOX) 的纳米载体。合成了尺寸为 3.2 nm 的柠檬酸稳定的 USIO NP，对其进行修饰以具有表面胺基团，并交联以获得 pH 响应性纳米团簇 (NC)。然后，将形成的 USIO NC 负载 DOX，并涂上癌症 CM，使其具有对巨噬细胞细胞摄取的抵抗性和同源癌细胞靶向特异性。在酸性肿瘤微环境中，具有主导T磁共振（MR）成像性能的pH响应性USIO NCs/DOX@CM可以解离形成具有T MR成像能力的单个USIO NP，同时快速释放DOX，从而实现动态T肿瘤的/T加权MR成像和化疗。此外，通过超声诱导的声孔效应，可以进一步增强动态磁共振成像和肿瘤化疗。设计的 USIO NCs/DOX@CM 可开发为多功能治疗诊断平台，用于不同癌症类型的超声增强靶向精确治疗诊断。