Work

A mitochondria targeted nitroreductase-sensitive self-immolative spacer as an efficient shuttle for uncharged amine-based molecules

Year: 2025

Type: article

Abstract: Mitochondria have emerged as critical therapeutic targets in a wide range of diseases. The detailed examination of this organelle, as well as the search for methods to efficiently address it, therefore, represent significant challenges. In this article, we present a simple and robust method for the functionalization of uncharged amine-based molecules to enable their intracellular transport and selective accumulation in mitochondria. To this end, we have synthesized a self-immolative spacer that is both sensitive to mitochondrial nitroreductase and incorporates a triphenylphosphonium vectorising moiety. To demonstrate the efficacy of this mitochondrial shuttling technology, we have designed, synthesized, and employed a fluorogenic probe that unambiguously validates the concept. An initial extension of this technology for therapeutic purposes is proposed through the intramitochondrial delivery of native doxorubicin, showing promising potential for overcoming drug resistance mechanisms.

Source: Chemical Science

DOI: 10.1039/d5sc03665h

Authors: Laurane Michel, Vincent Steinmetz, Sophia Godel-Pastre, Philippe Durand, Arnaud Chevalier

Institutions: Centre National de la Recherche Scientifique, Institut de Chimie des Substances Naturelles, Université Paris-Saclay

Language: English

Topic: Molecular Sensors and Ion Detection

Subfield: Spectroscopy

Field: Chemistry

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: diamond

Funders: Agence Nationale de la Recherche, Centre National de la Recherche Scientifique, Université Paris-Saclay