Controlled Release of a Micelle Payload via Sequential Enzymatic and Bioorthogonal Reactions in Living Systems

Angew Chem Int Ed Engl. 2019 May 6;58(19):6366-6370. doi: 10.1002/anie.201902137. Epub 2019 Mar 29.

Abstract

A bioorthogonal approach is explored to release the content of nanoparticles on demand. Exploiting our recently described click-and-release technology, we developed a new generation of cleavable micelles able to disassemble through a sequential enzymatic and bioorthogonal activation process. Proof-of-concept experiments showed that this new approach could be successfully used to deliver the substances encapsulated into micelles in living cells as well as in mice by two complementary targeted strategies.

Keywords: chemical biology; cleavable linkers; click chemistry; mesoionics; nanoparticles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes / chemistry
  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / therapeutic use
  • Cell Line, Tumor
  • Click Chemistry
  • Cyclooctanes / chemistry
  • Drug Liberation
  • Glucuronides / chemistry
  • Humans
  • Kinetics
  • Mice
  • Micelles*
  • Nanoparticles / chemistry
  • Neoplasms / drug therapy
  • Neoplasms / pathology
  • Pharmaceutical Preparations / chemistry
  • Pharmaceutical Preparations / metabolism*
  • Tetrazoles / chemistry
  • Transplantation, Heterologous

Substances

  • Alkynes
  • Antineoplastic Agents
  • Cyclooctanes
  • Glucuronides
  • Micelles
  • Pharmaceutical Preparations
  • Tetrazoles