Erythrocyte-membrane camouflaged manganese dioxide-polydopamine nanocarriers for doxorubicin delivery and MRI-visualized chemo-photothermal cancer therapy.

Abstract

Doxorubicin (DOX) chemotherapy is limited by systemic toxicity, poor tumor accumulation, and the acidic, hypoxic tumor microenvironment (TME). We developed MnO2-PDA-DOX@RBC/FA/PEG nanoparticles by coating manganese dioxide (MnO2) cores with polydopamine (PDA) for DOX loading and cloaking the particles with folic acid (FA)- and polyethylene glycol (PEG)-modified erythrocyte membranes. The nanosystem combined colloidal stability, erythrocyte-membrane-associated long circulation, FA-mediated tumor targeting, near-infrared photothermal conversion, and TME-responsive drug release. MnO2 catalyzed hydrogen peroxide decomposition to generate oxygen and consumed protons under acidic conditions, while acid-triggered MnO2 degradation produced Mn2⁺ for T1-weighted magnetic resonance imaging (MRI). In HepG2 cells, the nanoparticles enhanced DOX uptake, promoted lysosomal escape and mitochondrial accumulation, disrupted redox homeostasis, and strengthened apoptosis under 808 nm irradiation. In H22 tumor-bearing mice, MnO2-PDA-DOX@RBC/FA/PEG prolonged DOX circulation, reduced cardiac exposure, increased tumor accumulation, and achieved superior chemo-photothermal antitumor efficacy with reduced systemic inflammation. This biomimetic theranostic platform enables MRI- visualized, TME-responsive chemo-photothermal cancer therapy.