Tumor intracellular microenvironment-responsive nanoparticles for magnetically targeted chemotherapy

Abstract

Nanoparticles (NPs) with responsive modalities in biological microenvironments and external stimuli have received great attention as highly efficient and precise cancer therapy agents. In this study, tumor intracellular microenvironment-responsive NPs co-assembled from poly(ethylene glycol)-poly(aspartic acid) [PEG-P(Asp)] copolymer, doxorubicin (DOX), and superparamagnetic iron oxide NPs (SPIONs), termed as PEG-P(Asp)/DOX/SPIONs, were prepared for tumor intracellular microenvironment (enzyme and pH)-responsive and magnetically targeted chemotherapy. The NPs exhibited not only enzyme-responsive degradation in the presence of protease, but also triggered release of DOX at pH 5, which is an acidity similar to endolysosomal microenvironments in tumor cells. Furthermore, the PEG-P(Asp)/DOX/SPIONs showed a contrast effect in magnetic resonance imaging. In vitro viability assays showed that PEG-P(Asp)/DOX/SPIONs could effectively augment the cytocompatibility of DOX compared to free DOX without a change in magnetic forces. Fluorescence microscopy images indicated that the fabricated NPs efficiently increased the targeted uptake and release of DOX within cells. Overall, this hybrid NP system could be a favorable biomedical agent for effective tumor-targeted anti-cancer therapy.