AIE-Based Theranostic Agent: In Situ Tracking Mitophagy Prior to Late Apoptosis To Guide the Photodynamic Therapy

Abstract

Photodynamic therapy (PDT) takes advantage of reactive oxygen species (ROS) to trigger the apoptosis for cancer therapy. Given that cell apoptosis is a form of programmed cell death involved with multiple suborganelles and cancer cells are more sensitive to ROS than normal cells, early confirmation of the apoptosis induced by ROS would effectively avoid overtreatment. Herein, we highlight an aggregation-induced emission (AIE)-based theranostic agent (TPA3) to in situ dynamically track mitophagy prior to late apoptosis. TPA3 showed high specificity to autophagy vacuoles (AVs), of which appearance is the signature event of mitophagy during early apoptosis and delivered photocytotoxicity to cancer cells and skin cancer tumors in nude mice under irradiation of white light. Furthermore, in situ monitoring of the dynamical mitophagy process involved with mitochondria, AVs, and lysosomes was performed for the first time under confocal microscopy, providing a real-time self-monitoring system for assessing the curative effect prior to late apoptosis. This fluorescence imaging guided PDT witness great advances for applying in the clinical application.

Highly efficient singlet oxygen generation, two-photon photodynamic therapy and melanoma ablation by rationally designed mitochondria-specific near-infrared AIEgens

“…Furthermore, the Annexin V-FITC assay was performed aer the PDT treatment for detecting cell apoptosis. 58,59 Obvious cell apoptosis caused by DCQu under light with green PL in the cell membrane was observed, while the cells without light irradiation showed no obvious apoptotic behaviour (Fig. S32 †).…”

Modified Indulines: From Dyestuffs to In Vivo Theranostic Agents

“…1 H NMR spectra were recorded at room temperature on a Bruker AC250, a Bruker AC500 or on a JEOL ECS400 spectrometers operating at 250, 500 and 400 MHz, respectively. 13 C NMR spectra were recorded at room temperature on a Bruker AC250 or on a JEOL ECS400 spectrometers operating at 63 and 100 MHz, respectively. High-resolution mass spectrometry (HRMS) analysis was performed by the "Spectropole" of Aix-Marseille University.…”

“…1 H NMR (400 MHz, CDCl3): δ 9.27 (s, 1H), 9.12 (br s, 1H), 8.21 (br t, J = 4.8 Hz, 1H), 6.87 (d, J = 8.3 Hz, 1H), 6.00 (dd, J = 8.3, 2.2 Hz, 1H), 5.96 (d, J = 2.2 Hz, 1H), 5.69 (s, 1H), 3.77 (br s, 1H), 3.68 (br s, 1H), 3.13 (t, J = 7.2 Hz, 2H), 3.13 -3.05 (m, 2H), 3.00 (q, J = 6.1 Hz, 2H), 1.68 -1.52 (m, 6H), 1.45 -1.23 (m, 30H), 0.90 -0.84 (m, 9H). 13…”

“…1 H NMR (400 MHz, CD3CN): δ 7.78 (d, J = 9.2 Hz, 1H), 7.19 (dd, J = 9.2Hz, 1.7Hz, 1H), 6.96 (s, 1H), 6.89 (s, 1H), 6.52 (d, J = 1.7Hz, 1H), 6.24 (br t, J = 5.2 Hz, 1H), 6.18 (br s, 2H), 4.78 (br s, 1H), 4.54 (t, J = 8.1 Hz, 2H), 3.34 (td, J = 6.7 Hz, 6.0 Hz, 2H), 3.28 (td, J = 6.7 Hz, 5.2 Hz, 2H), 1.79 -1.67 (m, 4H), 1.64 -1.56 (m, 2H), 1.51 -1.30 (m, 30H), 0.91 -0.88 (m, 9H). 13…”

“…[1][2][3][4][5][6][7] As such, theranostic molecules are mainly constituted of an imaging unit combined to a therapeutic agent within the same platform. They can be divided into two families: i) nanoparticles and/or macromolecular materials/polymers in which the diagnostic and therapeutic units are adsorbed, conjugated, or aggregated; [8][9][10][11][12][13][14][15][16] ii) dual molecules, incorporating two distinct units (through a covalent bonding) for diagnosis and therapy. [17][18][19][20][21] These multifunctional molecules operate intracellularly and can be activated by external stimuli such as light.…”