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

ACS Appl Mater Interfaces. 2020 Jan 15;12(2):1988-1996. doi: 10.1021/acsami.9b15577. Epub 2020 Jan 2.

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.

Keywords: aggregation induced emission; early apoptosis; fluorescence imaging guided photodynamic therapy; mitophagy; self-monitoring.

MeSH terms

  • Animals
  • Apoptosis* / radiation effects
  • Autophagosomes / metabolism
  • Autophagosomes / radiation effects
  • Fluorescence
  • HeLa Cells
  • Humans
  • Lysosomes / metabolism
  • Lysosomes / radiation effects
  • Membrane Fusion / radiation effects
  • Mice, Nude
  • Mitophagy* / radiation effects
  • Optical Imaging
  • Photochemotherapy*
  • Reactive Oxygen Species / metabolism
  • Subcutaneous Tissue / pathology
  • Theranostic Nanomedicine*

Substances

  • Reactive Oxygen Species