Work

Fabrication of Redox‐Responsive Macromolecular Prodrug Nanoparticles and Studies on Their In Vitro Therapeutic Efficacy of Breast Cancer

Year: 2025

Type: article

Abstract: ABSTRACT The objective of this study is to fabricate a novel glutathione/redox dual‐responsibility macromolecular prodrug, naked PPHSD NPs, for efficiently tumor‐targeted delivery of doxorubicin (DOX) molecules and minimize their side effects. The precursor polymers, named PPH, were initially synthesized by a free radical polymerization, and then DOX molecules were conjugated onto the PPH polymers with disulfide bonds as linkages. The macromolecular prodrug nanoparticles (PPHSD NPs) exhibited a uniform size distribution and high standing stability in the neutral environment. Their negatively charged surfaces inhibited the PPHSD NPs from being absorbed by the plasma proteins, resulting in effectively delivering sufficient DOX molecules to tumors. After cellular internalization, the PPHSD NPs would quickly respond to the tumor microenvironment, such as high glutathione (GSH) concentration and reactive oxygen species (ROS). Subsequently, the disulfide bonds cleaved, resulting in the disassembly of the PPHSD NPs and DOX discharge. In vitro experiments confirmed the excellent anti‐tumor activity of the PPHSD NPs. Moreover, the biosafety tests demonstrated that the PPHSD NPs did not induce obvious lesions on organs and hematotoxicity, indicating their high biosafety. Collectively, it is expected that the redox‐responsible PPHSD NPs could play an important role in the therapy of tumors.

Source: Journal of Applied Polymer Science

DOI: 10.1002/app.57595