Biomimetic Aggregation‐Induced Emission Nanodots with Hitchhiking Function for T Cell‐Mediated Cancer Targeting and NIR‐II Fluorescence‐Guided Mild‐Temperature Photothermal Therapy

Abstract Photothermal therapy (PTT) holds potential as an alternative approach for effective cancer treatment since it exerts minimal side effects on normal tissues. However, the photothermal stimulation increases the expression of heat shock protein (HSP) in tumor cells, rendering the tumor cells insensitive to heat and thus constraining the effects of PTT. In this study, biomimetic aggregation‐induced emission (AIE) photothermal agents with hitchhiking ability (DC@BPBBT dots) are developed by coating the nanoaggregates of the NIR AIE polymeric photothermal agents with dendritic cell (DC) membranes. Notably, the inner nanoaggregate (BPBBT dots) holds bright second‐window near infrared (NIR‐II) fluorescence (quantum yield of up to 3.47%) and a high photothermal conversion performance (photothermal conversion efficiency of up to 30.5%), and the outer cell membrane can facilitate the hitchhiking of DC@BPBBT dots on endogenous T cells and enhance the tumor delivery efficiency by about 1.2 times. Furthermore, DC@BPBBT dots can activate and stimulate T cells in vivo to secrete cytokine tumor necrosis factor α (TNF‐α), which can reduce the expression of heat shock protein 70 (HSP70) to render tumor cells more sensitive to heat. This study not only provides an alternative heat shock protein inhibition strategy based on immune cell interactions but also provides a hitchhike approach for drug delivery in cancer photothermal immunotherapy.