Intelligent Tumor Microenvironment-Activated Multifunctional Nanoplatform Coupled with Turn-on and Always-on Fluorescence Probes for Imaging-Guided Cancer Treatment

Intrinsic tumor microenvironment (TME)-related therapeutic resistance and nontumor-specific imaging have limited the application of imaging-guided cancer therapy. Herein, a TME-responsive MnO 2 -based nanoplatform coupled with turn-on and always-on fluorescence probes was designed through a facile biomineralization method for imaging-guided photodynamic/chemodynamic/photothermal therapy (PDT/CDT/PTT). After the tumor-targeting delivery of the AuNCs@MnO 2 -ICG@AS1411 (AMIT) nanoplatform via aptamer AS1411, the TME-responsive dissociation of MnO 2 generated sufficient O 2 and Mn 2+ with the consumption of GSH for improving PDT efficacy and Fenton-like reaction-mediated CDT. Simultaneously, the released small-sized ICG and AuNCs facilitated PDT and PTT efficacy via the deep tumor penetration. Moreover, the turn-on fluorescence of AuNCs revealed the real-time TME-responsive MnO 2 degradation process, and the always-on ICG fluorescence enabled the in situ monitoring of the payload distribution in vitro and in vivo . The AMIT NPs also provided magnetic resonance and thermal imaging guidance for the enhanced PDT, CDT, and PTT. Therefore, this all-in-one nanosystem provides a simple and versatile strategy for multiple imaging-guided theranostic applications.