Glycosylated Multifunctional Nanoplatform Co‐Delivering Artemisinin: Synergizing NIR‐Responsive Phototherapy with Chemodynamic Therapy for Precision‐Targeted Tumor Theranostics

Phototherapy is promising because of its spatiotemporal precision, minimal invasiveness, and low systemic toxicity, but most antitumor delivery systems rely on EPR-mediated passive targeting and nonspecific uptake, resulting in suboptimal tumor drug accumulation and reduced efficacy. We innovatively developed a lactose-modified, self-assembled, and NIR-responsive type-I photosensitizer, BDPL, with precise HepG2-targeting ability. Multiglycosylation enables the efficient generation of O₂ ^-• via the regulation of carbohydrate‒carbohydrate interactions (CCIs) among neighboring lactose units in the nanoaggregates, enabling BDPLs to be used for NIR-responsive type I photodynamic therapy (PDT) and photothermal therapy (PTT). Concurrently, to address the inherent limitations of conventional phototherapy, specifically inadequate tissue penetration and profound tumor hypoxia, we engineered ABDPL@Fe NPs through the strategic loading of hydrophobic artemisinin (ARTE) with amphoteric BDPL followed by Fe(III) coordination, establishing a synergistic therapeutic platform for increased tumor suppression. This innovative nanoplatform serves as a nanogenerator of carbon-centered and hydroxyl radicals under hypoxic and light-deprived conditions, revealing significant potential for treating deep-seated tumors with hypoxic microenvironments. For the first time, we report a glycosylated NIR-activated nanoplatform that unleashes a ROS storm to disrupt tumor antioxidant defenses, inducing synergistic apoptosis-ferroptosis death. This strategy has antitumor efficacy and improves precision-targeted treatment.