Smart dual-responsive theranostic MUC1 aptamer-tagged macrophage cell membrane–coated hollow manganese dioxide for chemodynamic therapy and MR imaging of melanoma
摘要
Hollow manganese dioxide (HMnO2) nanoparticles offer significant potential for biomedical and biosensing applications. This study presents a pH- and glutathione (GSH) responsive biodegradable HMnO₂-based drug delivery system designed to enhance chemodynamic therapy through targeted drug release.
MethodsHMnO2 nanoparticles were synthesized with high doxorubicin hydrochloride (DOX) loading efficiency. The DOX-loaded HMnO2 was coated with macrophage cell membranes (MCM) to improve biocompatibility. A MUC1-targeting DNA aptamer was conjugated to develop the Apt-HMnO2-DOX-MCM construct. In vitro, assays evaluated DOX release under acidic and elevated GSH conditions and assessed Fenton-like catalytic activity. In vivo, efficacy was tested in B16F0 tumor-bearing C57BL/6 mice. Magnetic resonance imaging (MRI) capabilities were also investigated.
ResultsHMnO2 nanoparticles demonstrated a high DOX encapsulation efficiency of 94% ± 2.8 and a loading content of 38% ± 1.1. Apt-HMnO2-DOX-MCM significantly increased cytotoxicity cellular uptake and inhibited colony formation and migration in MUC1-overexpressing B16F0 cells. In vivo studies showed marked tumor size reduction compared to non-targeted controls. Both Apt-HMnO2-DOX-MCM and HMnO2-DOX-MCM functioned effectively as T1- and T2-weighted MRI contrast agents.
ConclusionThe Apt-HMnO2-DOX-MCM construct represents a promising biocompatible theranostic platform that combines targeted drug delivery with diagnostic imaging to potentiate chemodynamic cancer therapy.