One-Step Formulation of Targeted Aggregation-Induced Emission Dots for Image-Guided Photodynamic Therapy of Cholangiocarcinoma

ACS Nano. 2017 Apr 25;11(4):3922-3932. doi: 10.1021/acsnano.7b00312. Epub 2017 Apr 11.

Abstract

Photodynamic therapy (PDT) is a palliative technique that can improve median survival with minimal invasion for cholangiocarcinoma (CC) patients. An ideal photosensitizer (PS) is critical to guarantee the efficacy of PDT. However, conventional PSs have some obvious drawbacks, such as lack of specificity and easy aggregation in aqueous media that limit their further application in the clinic. We herein fully take advantage of a red emissive aggregation-induced emission (AIE) PS to fabricate integrin ανβ3 targeted organic AIE dots for image-guided PDT via a simple and straightforward one-step strategy. The obtained AIE dots exhibit high specificity to CC as well as excellent antitumor effect both in vitro and in vivo. Different from conventional PSs and previously reported PS-loaded nanostructures, the AIE dots do not suffer from aggregation-caused fluorescence quenching and reduction in reactive oxygen species production when the AIE PS molecules are in an aggregated state. The significant antitumor effect, as well as good biocompatibility and negligible toxicity, makes the AIE dots promising for future translational research in CC diagnosis and therapy.

Keywords: aggregation-induced emission; cholangiocarcinoma; photodynamic therapy; targeted fluorescence imaging; targeted therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bile Duct Neoplasms / diagnostic imaging
  • Bile Duct Neoplasms / drug therapy*
  • Cholangiocarcinoma / diagnostic imaging
  • Cholangiocarcinoma / drug therapy*
  • Humans
  • Integrin alphaVbeta3 / antagonists & inhibitors*
  • Integrin alphaVbeta3 / metabolism
  • Mice
  • Mice, Nude
  • Neoplasms, Experimental / diagnostic imaging
  • Neoplasms, Experimental / drug therapy
  • Optical Imaging
  • Photochemotherapy*
  • Photosensitizing Agents / therapeutic use*
  • Protein Aggregates / drug effects
  • Tumor Cells, Cultured

Substances

  • Integrin alphaVbeta3
  • Photosensitizing Agents
  • Protein Aggregates