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

Abstract 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 Fe 2 ⁺ 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 Fe 2 ⁺ 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 Fe 2 ⁺ 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.