Less is More: Asymmetric D‐A Type Agent to Achieve Dynamic Self‐Assembled Nanoaggregates for Long‐Acting Photodynamic Therapy

Abstract To enhance the phototheranostic performance, agents with high reactive oxygen species (ROS) generation, good tumor‐targeting ability, and prolonged retention are urgently needed. However, symmetric donor–acceptor (D–A) type agents usually produce spherical nanoaggregates, leading to good tumor targeting but inferior retention. Rod‐like nanoaggregates are desired to extend their retention in tumors; however, this remains a challenge. In particular, agents with dynamically changeable shapes that integrate merits of different morphologies are seldomly reported. Therefore, self‐assembled organic nanoaggregates with smart shape tunability are designed here using an asymmetric D–A type TIBT. The photoluminescence quantum yield in solids is up to 52.24% for TIBT. TIBT also exhibits high ROS generation in corresponding nanoaggregates (TIBT‐NCs). Moreover, dynamic self‐assembly in shape changing from nanospheres to nanorods occurrs in TIBT‐NCs, contributing to the enhancement of ROS quantum yield from 0.55 to 0.72. In addition, dynamic self‐assembly can be observed for both in vitro and in vivo, conferring TIBT‐NCs with strong tumor targeting and prolonged retention. Finally, efficient photodynamic therapy to inhibit tumor growth is achieved in TIBT‐NCs, with an inhibition rate of 90%. This work demonstrates that asymmetric D–A type agents can play significant roles in forming self‐assembled organic nanoaggregates, thus showing great potential in long‐acting cancer therapy.