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

Abstract

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 0.1Hz for 1.5h 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. © 2026 Wiley-VCH GmbH.