Six Birds with One Stone: Versatile Nanoporphyrin for Single‐Laser‐Triggered Synergistic Phototheranostics and Robust Immune Activation

Abstract Simultaneous photodynamic therapy (PDT) and photothermal therapy (PTT) can reduce the risks of drug leakage, body burden, and preparation complexity in traditional combination PDT/PTT. Here, a versatile nanoporphyrin (Pp18‐lipos) self‐assembled from lipid–purpurin 18 conjugates (Pp18‐lipids) and pure lipids is presented. The as‐prepared Pp18‐lipos with 2 mol% Pp18‐lipids can perform effective PDT and fluorescence imaging. The Pp18‐lipos with 65 mol% Pp18 can perform potent PTT and photoacoustic imaging. The chelation of Mn²⁺ endows the Pp18‐lipids‐Mn²⁺ a high T₁‐weighted magnetic resonance imaging contrast. Notably, pretreatment of low‐dose PDT facilitates the endocytosis and tumor accumulation of Pp18‐lipos, thus achieving synergistic PDT/PTT. Upon exposure to a single 705 nm‐laser, the combination of PDT/PTT achieves a significantly higher tumor growth inhibition rate than PDT or PTT alone. In addition, it is found that the synergistic PDT/PTT triggers more potent anti‐tumor immune response including tumor infiltration of immune cells and release of related cytokines.