A Planarity‐Hindrance Co‐Balance Strategy to Develop Antiparallel H‐Aggregates With Minimal Absorbance Blueshift for Type I Photodynamic Therapy

ABSTRACT

H‐aggregates offer intrinsic features for type I photodynamic therapy (PDT) by concurrently promoting triplet state formation and strengthening charge transfer ability. However, their exploitation remains limited by the inherently large absorption blueshift (usually >100 nm) arising from strong H‐type excitonic coupling in conventional parallel‐packed H‐aggregates, forcing short‐wavelength laser excitation with poor tissue penetration. Herein, this study reports a planarity‐hindrance co‐balance strategy to develop donor‐π‐acceptor‐based antiparallel‐packed H‐aggregates with minimal absorption blueshift for type I PDT. The results demonstrate that π‐bridge planarization drives H‐packing, while donor‐site steric tuning dictates the blueshift by modulating slipping angles and π‐π overlapping degree, and a steric threshold (Me/OMe) is identified beyond which blueshift becomes invariant. The optimized MTBSIC molecules form H‐aggregates with an exceptionally small blueshift of 15 nm over its monomers. MTBSIC H‐aggregates further display markedly enhanced type I ROS generation and improved photothermal conversion ability over their amorphous counterparts possessing similar monomeric photophysical properties. Mechanistic analyses reveal that H‐packing promotes both intersystem crossing and intermolecular charge transfer/separation, synergistically boosting type I ROS production. MTBSIC H‐aggregates further achieve potent tumor inhibition with high biocompatibility both in vitro and in vivo. This work establishes a generalizable molecular design paradigm for near‐monomer‐like H‐aggregates for high‐performance phototheranostics.