Modulating the cellular microenvironment with disulfide-containing nanoparticles as an auxiliary cancer treatment strategy

Abstract

Stimuli-responsive drug release nanoparticles are of particular interest due to their enhanced effects and reduced systemic toxicities in the area of cancer therapeutics. The effect of these nanoparticles on the cellular microenvironment has not yet been clearly defined. In this context, redox-responsive nanoparticles were synthesized with disulfide-containing linkages. These nanoparticles depleted the cellular GSH level and modulated the cellular redox microenvironment to more oxidizing conditions. The resulting drug-encapsulated nanoparticles showed improved cytotoxicity, apoptosis, and invasion inhibition of metastatic cancer cells. Moreover, these improvements had a direct correlation with the cellular redox status modulated by nanoparticles. The present study provides a new strategy for designing redox-responsive drug carriers to improve the sensitivity of cells to anticancer drugs and enhance the therapeutic efficacy in metastatic cancer.