The effort of incorporating therapeutic drugs with imaging agents has been one of the mainstreams of nanomedicine, which holds great promise in cancer treatment in terms of monitoring therapeutic drug activity and evaluating prognostic index. However, it is still technically challenging to develop nanomedicine endowing a spatiotemporally controllable mechanism of drug release and activatable imaging capability. Here, we developed a yolk-shell type of GSH-responsive nanovesicles (NVs) in which therapeutic drug (Doxorubicin, DOX) and magnetic resonance imaging (MRI) contrast agent (ultrasmall paramagnetic iron oxide nanoparticles, USPIO NPs) formed complexes (denoted as USD) and were encapsulated inside the NVs. The formation of USD complexes is mediated by both the electrostatic adsorption between DOX and poly(acrylic acid) (PAA) polymers and the DOX-iron coordination effect on USPIO NPs. The obtained USD NVs showed a unique yolk-shell structure with restrained drug activity and quenched T₁ MRI contrast ability which, on the other hand, can respond to glutathione (GSH) and lead to drug release and T₁ contrast activation in a spatiotemporally concurrent manner. Furthermore, the USD NVs exhibited great potential to kill HCT116 cancer cells in vitro and effectively inhibit the tumor growth in vivo. This study may shed light on the design of sophisticated nanotheranostics in precision nanomedicine.

将治疗药物与显像剂相结合已成为纳米医学的主流之一，在监测治疗药物活性和评估预后指标方面，其在癌症治疗中具有广阔的前景。然而，开发具有时空可控药物释放机制和可激活成像能力的纳米药物在技术上仍然具有挑战性。在这里，我们开发了一种卵黄壳型 GSH 响应性纳米囊泡 (NVs)，其中治疗药物（阿霉素，DOX）和磁共振成像 (MRI) 造影剂（超小顺磁性氧化铁纳米颗粒，USPIO NPs）形成复合物（表示为USD）并封装在 NV 内。USD复合物的形成是由DOX和聚丙烯酸(PAA)聚合物之间的静电吸附以及USPIO NPs上的DOX-铁配位效应介导的。获得的 USD NVs 显示出独特的蛋黄壳结构，具有抑制药物活性和淬灭T ₁ MRI 对比能力，另一方面，它可以响应谷胱甘肽（GSH）并导致药物释放和时空并发的T ₁对比激活方式。此外，USD NVs表现出在体外杀死HCT116癌细胞并在体内有效抑制肿瘤生长的巨大潜力。这项研究可能有助于揭示精密纳米医学中复杂纳米治疗学的设计。