Rational Design of IR820‐ and Ce6‐Based Versatile Micelle for Single NIR Laser–Induced Imaging and Dual‐Modal Phototherapy

Abstract Phototherapy as a promising cancer diagnostic and therapeutic strategy has aroused extensive attention. However, single‐wavelength near‐infrared (NIR) light–triggered combinational treatment of photothermal therapy (PTT) and photodynamic therapy (PDT) is still a great challenge. Herein, a multifunctional micelle activated by a single‐wavelength laser for simultaneous PTT and PDT as well as fluorescence imaging is developed. Briefly, new indocyanine green (IR820) is conjugated to d ‐α‐tocopheryl polyethylene glycol 1000 succinate (TPGS) via the linker 6‐aminocaproic acid, and then, chlorin e6 (Ce6) is encapsulated into the micelles formed by TPGS–IR820 conjugates to fabricate TPGS–IR820/Ce6 micelles. As the well‐designed TPGS–IR820 conjugate shares a similar peak absorption wavelength with Ce6, this micelle can be applied with a single NIR laser (660 nm). The stable micelles exhibit excellent photothermal conversion efficiency in vitro and in vivo as well as high singlet oxygen generation capacity in tumor cells. After efficient cellular internalization, the as‐prepared micelles display outstanding anticancer activity upon single NIR laser irradiation in vitro and in vivo. Furthermore, TPGS–IR820/Ce6 micelles show negligible systemic toxicity. The highly safe and effective TPGS–IR820/Ce6 micelles can offer an innovative strategy to construct single NIR light–induced PTT and PDT combined phototherapy nanoplatforms via suitable modification of organic phototherapeutic agents.