Self‐Assembled Protonated Porphyrin Dimer Nanoparticles with an 83.7% Near‐Infrared Photothermal Conversion Efficiency for Antitumor Therapy

Abstract Despite the immense potential of near‐infrared photothermal therapy (NIR PTT) for tumor treatment, the development of photothermal agents (PTAs) with high photothermal conversion efficiency (PCE) remains a substantial challenge. Here, a “protonation‐manipulation molecular self‐assembly” strategy is presented that precisely regulates the protonation of the pyrrole nitrogen in 5,10,15,20‐tetra(4‐aminophenyl)porphyrin (TAPP), while maintaining the availability of the lone pair electrons on the nitrogen atoms in the aniline substituents. The resulting protonated dimers facilitate the formation of a robust saddle‐shaped conformation and a quinone‐like resonance structure, which subsequently self‐assemble into near‐infrared nanoparticles (NIR NPs). These protonated dimers enhance intermolecular exciton coupling, significantly improving absorption in the near‐infrared region. The photoexcitation process of TAPP NIR NPs is primarily governed by non‐radiative transitions, achieving an impressive PCE of up to 83.7%, markedly surpassing that of organic PTAs such as dopamine and traditional porphyrin derivatives. In vitro and in vivo studies demonstrate that NIR NPs effectively eliminate tumor cells while exhibiting excellent biocompatibility. This work represents a significant advancement in performance optimization from the spectral regulation of supramolecular photosensitizers, introducing innovative methodologies for the design of aromatic nitrogen‐containing PTAs functional molecules.