臭名昭著的肿瘤微环境（TME）通常在光疗进展过程中变得更加恶化，从而阻碍了抗肿瘤功效。为了克服这个问题，我们在此报告了改善和适应性纳米粒子（TPASIC-PFH@PLGA NPs），它同时逆转缺氧TME并将光活性从光热主导状态切换到光动力主导状态，以最大化光疗效果。 TPASIC-PFH@PLGA NPs 的设计是将富氧液体全氟己烷 (PFH) 纳入颗粒内微环境中，以调节 AIE 光敏剂 TPASIC 的分子内运动。 TPASIC 具有独特的聚集增强活性氧 (ROS) 生成功能。 PFH的掺入使TPASIC处于初始分散状态，从而促进活跃的分子内运动和光热转换效率。而 PFH 挥发会导致纳米颗粒塌陷并形成紧密的 TPASIC 聚集体，从而大大提高 ROS 生成效率。因此，PFH 的掺入不仅目前可以促进 TPASIC 的光热和光动力功效并增加瘤内氧水平，而且还使智能光热到光动力开关能够最大限度地提高光疗性能。 PFH和AIE光敏剂的结合最终提供了比具有固定光热和光动力功效的传统光治疗剂更优异的抗肿瘤效果。这项研究提出了一种新的纳米工程策略来改善 TME 并调整治疗方式以适应改变后的 TME，从而实现先进的抗肿瘤应用。版权所有 © 2024 Elsevier Ltd。保留所有权利。

The notorious tumor microenvironment (TME) usually becomes more deteriorative during phototherapeutic progress that hampers the antitumor efficacy. To overcome this issue, we herein report the ameliorative and adaptive nanoparticles (TPASIC-PFH@PLGA NPs) that simultaneously reverse hypoxia TME and switch photoactivities from photothermal-dominated state to photodynamic-dominated state to maximize phototherapeutic effect. TPASIC-PFH@PLGA NPs are designed by incorporating oxygen-rich liquid perfluorohexane (PFH) into the intraparticle microenvironment to regulate the intramolecular motions of AIE photosensitizer TPASIC. TPASIC exhibits a unique aggregation-enhanced reactive oxygen species (ROS) generation feature. PFH incorporation affords TPASIC the initially dispersed state, thus promoting active intramolecular motions and photothermal conversion efficiency. While PFH volatilization leads to nanoparticle collapse and the formation of tight TPASIC aggregates with largely enhanced ROS generation efficiency. As a consequence, PFH incorporation not only currently promotes both photothermal and photodynamic efficacies of TPASIC and increases the intratumoral oxygen level, but also enables the smart photothermal-to-photodynamic switch to maximize the phototherapeutic performance. The integration of PFH and AIE photosensitizer eventually delivers more excellent antitumor effect over conventional phototherapeutic agents with fixed photothermal and photodynamic efficacies. This study proposes a new nanoengineering strategy to ameliorate TME and adapt the treatment modality to fit the changed TME for advanced antitumor applications.Copyright © 2024 Elsevier Ltd. All rights reserved.