Abstract

A versatile theranostic agent that integrated with therapeutic and diagnostic functions is extremely essential for cancer theranostic. Herein, a multifunctional theranostic nanoplatform (PFP@MPDA-DOX) based on perfluoropentane (PFP) encapsulated mesoporous polydopamine (MPDA) is elaborately designed, followed by gating of drug doxorubicin (DOX) for preventing cargo leaking. The MPDA with pH-responsive biodegradation behavior was served as nanocarrier, which also endows the nanoplatform with a large cavity for PFP filling. The nanoparticles were then gated with DOX molecule by Michael addition and/or Schiff base reaction to shield the leaking of PFP during the blood circulation before the tumor tissue is reached. Also, such nanotheranostic exhibits high photothermal conversion efficiency of 45.6%, which can act as an intelligent nanosystem for photothermal therapy (PTT) and photoacoustic (PA) imaging. Moreover, the liquid-gas phase transition of PFP arising upon exposure to an 808 nm laser and thus produced the bubbles for ultrasound (US) imaging. The subsequent PFP@MPDA-DOX-mediated synergetic chemotherapy (contributed by the DOX gatekeeper) and PTT (contributed by the MPDA) shows excellent anticancer activity, which has been systematically evaluated both in vitro and in vivo. All these positive results certify that the facile incorporation of the antitumor drug gatekeeper and MPDA into one theranostic nanoplatform shows general potential for multimode PA/US imaging and combination chemotherapy/PTT of tumors.

 抽象的

集成治疗和诊断功能的多功能治疗诊断剂对于癌症治疗诊断极为重要。本文精心设计了基于全氟戊烷（PFP）封装介孔聚多巴胺（MPDA）的多功能治疗诊断纳米平台（PFP@MPDA-DOX），然后对药物阿霉素（DOX）进行门控以防止货物泄漏。具有pH响应性生物降解行为的MPDA作为纳米载体，这也赋予纳米平台一个用于PFP填充的大空腔。然后通过迈克尔加成和/或希夫碱反应用 DOX 分子对纳米颗粒进行门控，以在到达肿瘤组织之前防止血液循环过程中 PFP 的泄漏。此外，这种纳米治疗仪表现出高达45.6%的光热转换效率，可以作为光热治疗（PTT）和光声（PA）成像的智能纳米系统。此外，PFP 在暴露于 808 nm 激光时会发生液-气相变，从而产生用于超声 (US) 成像的气泡。随后的PFP@MPDA-DOX介导的协同化疗（由DOX看门人贡献）和PTT（由MPDA贡献）显示出优异的抗癌活性，并在体外和体内进行了系统评估。所有这些积极结果证明，将抗肿瘤药物守门人和 MPDA 轻松整合到一个治疗诊断纳米平台中，显示出多模式 PA/US 成像和肿瘤联合化疗/PTT 的普遍潜力。