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.