Peroxynitrite-Responsive Near-Infrared Fluorescent Imaging Guided Synergistic Chemo-Photodynamic Therapy via Biomimetic Metal-Organic Frameworks.

Abstract

Peroxynitrite (ONOO-) plays a crucial role in maintaining cellular redox homeostasis and regulating diffusive processes, cellular transport, and signal transduction. Extensive studies have revealed that increased ONOO- levels during tumor progression are associated with heightened levels of oxidative stress. However, current methods lack noninvasive visualization, immediate reporting, and highly sensitive fluorescence sensing. In light of this, we have designed a biomimetic fluorescent nanoplatform, named Z-C-T@CM, for peroxynitrite-responsive near-infrared fluorescent imaging guided cancer treatment. The nanoplatform comprises tetrakis(4-carboxyphenyl) porphyrin (TCPP) and curcumin (CCM) encapsulated within a zeolitic imidazolate framework-8 (ZIF-8), which is coated with a mouse breast cancer cell membrane for enhanced biocompatibility and targeting, while evading immune clearance. In vitro experimental results demonstrate that the as-prepared nanoplatform exhibits enhanced near-infrared fluorescence emission upon exposure to ONOO-, indicating a significant potential for noninvasive in vivo imaging of ONOO- during tumor progression. Additionally, Z-C-T@CM readily degrades in the tumor microenvironment, releasing TCPP and CCM, enabling a synergistic chemo-photodynamic therapy with near-infrared illumination. Further investigations indicate that Z-C-T@CM efficiently stimulates a tumor immune response and facilitates therapeutic efficiency. Collectively, this work introduces a novel noninvasive strategy for ONOO- detection, shedding new light on the integration of cancer diagnosis and efficient treatment.