A Water-Stable and Red-Emissive Radical Cation for Mutp53 Cancer Therapy

Angew Chem Int Ed Engl. 2022 Nov 14;61(46):e202212671. doi: 10.1002/anie.202212671. Epub 2022 Oct 17.

Abstract

Compared with conventional closed-shell fluorophores, radical cations provide an opportunity for development of red-to-NIR fluorophores with small sizes and easy preparation. However, most radical cations reported in the literature suffer from poor stability in water solution and are almost non-emissive. To tackle this challenge, we herein develop a deep-red-emissive and water-stable pyrrole radical cation P⋅+ -DPA-Zn, which can be easily generated from P-DPA-Zn by air oxidation. The deep-red-emissive P⋅+ -DPA-Zn can be used for imaging-guided mitochondria-targeted delivery of Zn2+ into cancer cells to promote mutant p53 proteins degradation and abrogate mutp53-manifested gain of function, including reduced chemotherapy resistance, inhibited cancer cell migration, decreased tumor cell colony and sphere formation. The water-stable and deep-red emissive pyrrole radical cation is thus promising for cancer theranostic applications.

Keywords: Fluorescence; Mitochondria; Mutp53; Radical Cation; Zinc Ion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cations / metabolism
  • Humans
  • Mutant Proteins / metabolism
  • Neoplasms* / drug therapy
  • Neoplasms* / pathology
  • Pyrroles
  • Tumor Suppressor Protein p53 / metabolism
  • Water* / metabolism

Substances

  • Water
  • Tumor Suppressor Protein p53
  • Mutant Proteins
  • Cations
  • Pyrroles