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

Abstract

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 potential for finely controlled PDT with good biosafety and broad application prospects in individual therapy, which may inspire the development of precision medicine.

Reactive Species-Activatable AIEgens for Biomedical Applications

“…PA imaging possesses the merits of good penetration depth and excellent spatial resolution, which has complementary advantages with fluorescence technique, thus, integration of PA imaging and fluorescence could greatly improve the diagnostic outcome [ 118 , 119 ]. Qu, Feng, and coworkers reported an activatable system for dual-modal imaging-guided PDT and self-reporting therapeutic process [ 120 ]. As displayed in Figure 5 , the nanoplatform was composed of an AIEgen with ROS-recognition phenylboronate moiety and a photosensitizer ZnPc.…”

PEG‐Polymer Encapsulated Aggregation‐Induced Emission Nanoparticles for Tumor Theranostics

“…[106][107][108][109][110][111][112] In addition to fluorescence performance, AIEgens have strong ROS generation ability and good photothermal conversion efficiency, so they can also be used for disease treatment. [113][114][115][116] AIEgens are not limited to treatment of tumor, but also have great potential in the field of antibacterial therapy. [117][118][119] A series of combination therapies derived from AIEgens also have great clinical transformation potential.…”

Molecularly engineered AIEgens with enhanced quantum and singlet-oxygen yield for mitochondria-targeted imaging and photodynamic therapy

“…[1][2][3][4][5] In recent years, FI-guided photodynamic therapeutic (PDT) agents and materials have been developed for cancer therapy and exhibit signicantly reduced side effects that are typically associated with traditional chemo-and radiotherapeutic drugs. [6][7][8][9][10][11] This is because the incorporation of uorescence and PDT into one single molecule can enable the positional monitoring in cells and in vivo, where cytotoxicity is only activated when an external, non-invasive light source is applied. Among all types of FI and PDT-active agents, organic dyes are advantageous in terms of the readily tunable photophysical properties using simple structural modications.…”