An Activatable Theranostic Nanoprobe for Dual-Modal Imaging-Guided Photodynamic Therapy with Self-Reporting of Sensitizer Activation and Therapeutic Effect

作者：Zhongtao Zhang, Ruyi Wang, Renjie Luo, Jiaxin Zhu, Xiaoxian Huang, Wenyuan Liu, Fulei Liu, Feng Feng, Wei Qu · 发表于：ACS Nano · 年份：2021 · DOI：10.1021/acsnano.0c10916 · 被引用次数：52 · 研究领域：Nanoplatforms for cancer theranostics、Luminescence and Fluorescent Materials、Photodynamic Therapy Research Studies

Intelligent systems that offer traceable cancer therapy are highly desirable for precision medicine. Although photodynamic therapy (PDT) has been approved in the clinic for decades, determining where the tumor is, when to irradiate, and how long to expose to light still confuse the clinicians. Patients are always suffering from the phototoxicity of the photosensitizer in nonmalignant tissues. Herein, an activatable theranostic agent, ZnPc@TPCB nanoparticles (NPs), is prepared by doping a photosensitizer, ZnPc, with an aggregation-induced emission probe, TPCB. The assembled or disassembled ZnPc@TPCB NPs in various phases have behaved differently in fluorescence intensity, photoacoustic (PA) signals, and PDT efficiency. The intact nanoparticles are non-emissive in aqueous media while showing strong PA signals and low PDT efficiency, which can eliminate the phototoxicity and self-monitor their distribution and image the tumors’ location. Disassembling of the NPs leads to the release of ZnPc and its red fluorescence turn-on to self-report the photosensitizer’s activation. Upon light irradiation, the reactive oxygen species (ROS) generated by ZnPc can induce cell apoptosis and activate the ROS sensor, TPCB, which will yield intense orange-red fluorescence and instantly predict the therapeutic effect. Moreover, enhanced PDT efficacy is achieved via the GSH-depleting adjuvant quinone methide produced by the activated TPCB. The well-designed ZnPc@TPCB NPs have shown promising potenti...