Suppressing Reverse Intersystem Crossing by Confining Organic Molecules within LDH Interlayers for Near‐Infrared‐II Photodynamic Immunotherapy

Abstract

Abstract Photodynamic therapy (PDT) leveraging near‐infrared‐II (NIR‐II) light holds promise for deep‐tissue cancer treatment, yet conventional photosensitizers (PSs) suffer from low singlet oxygen ( 1 O 2 ) quantum yields due to inefficient intersystem crossing (ISC) and short‐lived triplet states, hindering PDT effectiveness and subsequent immunogenic cell death (ICD) induction. Herein, a dual‐optimized PS is reported by intercalating I‐functionalized isophthalic acid (I‐IPA) into ZnAl‐LDH interlayers (LDH@I‐IPA) for NIR‐II PDT/immunotherapy. LDH‐mediated confinement effect not only narrows the bandgap for effective NIR‐II excitation, but also prolongs its triplet lifetime by 3 orders of magnitude through suppressing reverse intersystem crossing (RISC). Combined with I‐induced heavy‐atom effect promoting ISC, LDH@I‐IPA achieves a record‐high relative 1 O 2 quantum yield of 1.89. After polyethylene glycol (PEG) modification, LDH@I‐IPA‐PEG demonstrates potent tumor apoptosis and ICD, suppressing primary/metastatic tumors by 99.5%/52.2% through dendritic cell maturation, macrophage polarization, and cytotoxic T‐cell activation. Theoretical calculations and transcriptomic analysis confirm bandgap engineering, RISC inhibition, and immune pathway regulation.