Trojan Horse‐Like Nano‐AIE Aggregates Based on Homologous Targeting Strategy and Their Photodynamic Therapy in Anticancer Application

Photodynamic therapy (PDT) has become a promising candidate for cancer theranostics; however, traditional photosensitizers (PSs) usually exhibit weak fluorescence and poor reactive oxygen species (ROS) generation efficiency when aggregated. Recently, aggregation‐induced emission (AIE) luminogens have shown great potential in the development of novel PSs owing to their excellent aggregation‐induced ROS generation (AIG‐ROS) activity. However, there are still concerns that must be addressed. In this study, two near‐infrared (NIR) emitters (PI and PTI) are synthesized with AIG‐ROS characteristic. PTI exhibit a valuable redder emission with more effective intersystem crossing (ISC) process than PI. The two AIE‐active PSs show excellent lipid droplet (LD)‐specific targeting ability. The detailed therapeutic mechanism of PDT in LDs specificity is also investigated. The mechanism of oxidation of polyunsaturated fatty acids (PUFAs) in LDs to form toxic lipid peroxides (LPOs) and thereby causing cellular ferroptosis is confirmed first. Homologous targeting is also used to achieve tumor targeting via coating PSs with active cancer cell membranes. Biomimetic aggregates exhibit good targeting ability, and an improved PDT antitumor effect via AIG‐ROS activity. These findings offer a clear route to develop advanced PSs with good targeting specificity. A template has also been provided for studying the therapeutic mechanism of AIE‐active PSs.