Engineering Aptamer-Guided and Glutathione-Depleted Metal–Organic Framework Nanoinducer for Cancer Dual Phototherapy

In emerging strategies for localized tumor therapy, FDA-approved indocyanine green (ICG) is a promising candidate for phototherapy. Despite its potential, ICG's application is hindered by aqueous instability, intracellular antioxidant scavenging, and rapid clearance, necessitating nanomaterial-based formulations. Herein, a multifunctional nanoplatform integrating ICG into a glutathione (GSH)-responsive metal–organic framework (MOF) functionalized with AS1411 aptamers (AS1411@ICG@MOF, MIA) for stimuli-responsive delivery and intracellular redox regulation is developed. Constructed with a GSH-degradable MOF core for ICG encapsulation and an AS1411 aptamer shell for nucleolin targeting, MIA enables active tumor cell accumulation. Under laser irradiation, ICG acts as both a photosensitizer and photothermal agent, generating reactive oxygen species (ROS) and heat for synergistic photodynamic therapy/photothermal therapy (PDT/PTT). Thereout, GSH-triggered MOF disintegration facilitates intracellular ICG release, overcoming bioavailability challenges and GSH-mediated ROS consumption. Moreover, mild PTT minimizes off-target thermal injury while enhancing PDT via GSH depletion. Taken together, through aptamer-targeted delivery and GSH-responsive degradation, MIA achieves spatiotemporal control of ROS amplification and mild PTT, offering a promising strategy for synergistic cancer therapy.