Specific Targeting, Imaging, and Ablation of Tumor-Associated Macrophages by Theranostic Mannose-AIEgen Conjugates

Anal Chem. 2019 May 21;91(10):6836-6843. doi: 10.1021/acs.analchem.9b01053. Epub 2019 May 1.

Abstract

Tumor-associated macrophages (TAMs) that exist in tumor microenvironment promote tumor progression and have been suggested as a promising therapeutic target for cancer therapy in preclinical studies. Development of theranostic systems capable of specific targeting, imaging, and ablation of TAMs will offer clinical benefits. Here we constructed a theranostic probe, namely, TPE-Man, by attaching mannose moieties to a red-emissive and AIE (aggregation-induced emission)-active photosensitizer. TPE-Man can specifically recognize a mannose receptor that is overexpressed on TAMs by the sugar-receptor interaction and enables fluorescent visualization of the mannose-receptor-positive TAMs in high contrast. The histologic study of mouse tumor sections further verifies TPE-Man's excellent targeting specificity being comparable with the commercial mannose-receptor antibody. TAMs can be effectively eradicated upon exposure to white light irradiation via a photodynamic therapy effect. To our knowledge, this is the first small molecular theranostic probe for TAMs that revealed combined advantages of low cost, high targeting specificity, fluorescent light-up imaging, and efficient photodynamic ablation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzylidene Compounds / chemical synthesis
  • Benzylidene Compounds / pharmacology*
  • Benzylidene Compounds / radiation effects
  • Benzylidene Compounds / toxicity
  • Macrophages / drug effects*
  • Mannosides / chemical synthesis
  • Mannosides / pharmacology*
  • Mannosides / radiation effects
  • Mannosides / toxicity
  • Mice
  • Photochemotherapy / methods
  • Photosensitizing Agents / chemical synthesis
  • Photosensitizing Agents / pharmacology*
  • Photosensitizing Agents / radiation effects
  • Photosensitizing Agents / toxicity
  • Rats, Sprague-Dawley
  • Theranostic Nanomedicine / methods

Substances

  • Benzylidene Compounds
  • Mannosides
  • Photosensitizing Agents