Förster Resonance Energy Transfer Nanobullet for Photoacoustic Imaging and Amplified Photothermal‐Photodynamic Therapy of Cancer

Abstract Synergistic photodynamic and photothermal therapy (PDT‐PTT) has emerged as an appealing effective antitumor approach. However, clinical utilization of PDT‐PTT is plagued by aggregation‐caused photobleaching, sequential double irradiations, unsatisfying balance between single oxygen ( 1 O 2 ) quantum yield and photothermal conversion efficiency. Here, an anchored tumor‐homing cell‐penetrating peptide (PEGA‐ p VEC) and PANI‐ES/HMME loaded FRET nanobullet (AHP‐P) are reported. Within nanobullet, HMME (donor) and PANI‐ES (acceptor) spontaneously form a förster resonance energy transfer (FRET) pair. Upon 660 nm laser irradiation, HMME convert near‐infrared fluorescence (NIRF) to PANI, thus produce FRET‐amplified photoacoustic imaging guided PTT. In addition, AHP‐P with pH‐sensitivity can gradually release HMME within acidic tumor environment, boosts the 1 O 2 regeneration alongside with highly efficient photothermal conversion for photoinduced cancer PTT‐PDT. Furthermore, the AHP‐P nanobullet can home in on the tumor site and penetrate into cytoplasm through PEGA‐ p VEC, inducing remarkable tumor regression with an ≈80% tumor volume reduction and decreased skin phototoxicity in vivo during FRET‐amplified PTT‐PDT.