NIR‐II D–A–D‐Type Small‐Molecule Coordination with Carboxylatopillar[5]Arene: a Multifunctional Phototheranostic for Low‐Temperature NIR‐II Photothermal/Platinum‐Based/Chemodynamic Combination Cancer Immunotherapy

Low-temperature second near-infrared region (NIR-II) photothermal therapy (PTT) has shown significant potential in minimizing damage to normal tissues and reducing inflammation. However, it still faces challenge of insufficient immune response. Thus, a multifunctional phototheranostic nanoparticle (BDPB/Pt/Fe@P[5]) is developed by co-loading BDPB, CDHPt, and Fe²⁺ with a pH-sensitive lipid DSPE-PEOz2K. The carboxylatopillar[5]arene (CP[5]) used to construct this nanoparticle exhibits strong host-guest recognition with pyridine salts, alleviating aggregation caused quench (ACQ) effect and enhancing the NIR-II emission of the donor-acceptor-donor (D-A-D)-type organic small molecule (BDPB). CP[5] provides suitable vehicles for encapsulating platinum (IV) prodrugs (CDHPt) and Fe²⁺ ions via metal coordination for controllable reactive oxygen species (ROS) release. Under low-intensity NIR-II laser irradiation and an acidic tumor microenvironment, the nanoparticles degrade, releasing CDHPt and Fe²⁺ ions for platinum-based therapy and chemodynamic therapy (CDT). CDHPt facilitates the direct production of superoxide anions (O₂·⁻) from O₂ and partially converts it into the highly cytotoxic hydroxyl radicals, thereby promoting the Fenton reaction process. The therapeutic efficacy is further synergized by immunogenic cell death (ICD) effect.