Injectable Optoelectronic Probe With In Situ Photoactivation and ROS Monitoring for Oxygen‐Dependent Metronomic Photodynamic Cancer Therapy

Photodynamic therapy (PDT) offers an effective and minimally invasive approach to cancer treatment; however, its efficacy is intrinsically constrained by limited light penetration, which fails to target deep tumor tissues, and treatment-induced hypoxia arising from the reduction in intratumoral oxygen levels. Here, we report an injectable optoelectronic probe integrating microscale light-emitting diodes (microLEDs) to enable low-frequency metronomic PDT (mPDT), together with a microLED-photodetector system for real-time, in situ oxygen monitoring. We engineered light-activatable prodrug nanoparticles (PNPs) composed of verteporfin (VPF), a cathepsin B-cleavable peptide (FRRG), and doxorubicin (DOX). The self-assembled VPF-FRRG-DOX prodrug forms stable nanoparticles via π-π stacking, remaining inactive under physiological conditions but releasing and activating VPF and DOX in cathepsin B-overexpressing cancer cells during mPDT. In colon tumor-bearing mice, PNPs showed high tumor accumulation via enhanced permeability and retention (EPR) effect, while the microLED-photodetector probe monitored intratumoral in situ oxygen dynamics. Periodic oxygen depletion and recovery at 0.1 Hz for 1.5 h significantly improved therapeutic efficacy (p = 0.0047) compared with continuous PDT. Collectively, oxygen-guided mPDT combined with light-activatable PNPs provides a minimally invasive strategy for synergistic chemo-photodynamic therapy of deep tumors, with favorable systemic and local biocompatibility.