Photodynamic therapy (PDT) has long been recognized to be a promising approach for cancer treatment. However, the high oxygen dependency of conventional PDT dramatically impairs its overall therapeutic efficacy, especially in hypoxic solid tumors. Exploration of distinctive PDT strategy involving both high-performance less-oxygen-dependent photosensitizers (PSs) and prominent drug delivery system is an appealing yet significantly challenging task. Herein, a precise nuclear targeting PDT protocol based on type-I PSs with aggregation-induced emission (AIE) characteristics is fabricated for the first time. Of the two synthesized AIE PSs, TTFMN is demonstrated to exhibit superior AIE property and stronger type-I reactive oxygen species (ROS) generation efficiency owing to the introduction of tetraphenylethylene and smaller singlet–triplet energy gap, respectively. With the aid of a lysosomal acid-activated TAT-peptide-modified amphiphilic polymer poly(lactic acid)12k–poly(ethylene glycol)5k–succinic anhydride-modified TAT, the corresponding TTFMN-loaded nanoparticles accompanied with acid-triggered nuclear targeting peculiarity can quickly accumulate in the tumor site, effectively generate type-I ROS in the nuclear region and significantly suppress the tumor growth under white light irradiation with minimized systematic toxicity. This delicate “Good Steel Used in the Blade” tactic significantly maximizes the PDT efficacy and offers a conceptual while practical paradigm for optimized cancer treatment in further translational medicine.
Li Jiangao,Niu Niu,Wang Deliang,Liu Xue,Qin Yi,Wang Lei,Tang Ben Zhong,Wang Dong
Exploration of single molecular species synchronously featured by long excitation/emission wavelength, accurate diagnosis, and effective therapy, remains supremely appealing to implement high-performance cancer phototheranostics. However, those previously established phototheranostic agents are undiversified and stereotyped in terms of structural skeleton, and generally exhibit insufficient phototheranostic outcomes. Herein, we innovatively utilized indanone-condensed thiadiazolo[3,4-g]quinoxaline (ITQ) as electron acceptor to construct novel photosensitizer with second near-infrared (NIR-II) emission. Experimental study and theoretical calculation demonstrated that comparing with the counterparts constituting by widely employed NIR-II building block benzobisthiadiazole (BBTD) and 6,7-diphenylthiadiazoloquinoxaline (DPTQ), ITQ-based photosensitizer (TITQ) showed superior aggregation-induced emission (AIE) characteristics, much stronger type-I reactive oxygen species (ROS) production, and prominent photothermal conversion capacity. Furthermore, TITQ nanoparticles with excellent biocompatibility were capable of effectively accumulating in the tumor site and visualizing tumor through fluorescence-photoacoustic-photothermal trimodal imaging with highly spatiotemporal resolution, and completely eliminating tumor by type-I photodynamic-photothermal therapy.
危险品化学品经营许可证（带存储）