A Catalase-Like Metal-Organic Framework Nanohybrid for O2 -Evolving Synergistic Chemoradiotherapy

Abstract

Tumor hypoxia, the "Achilles' heel" of current cancer therapies, is indispensable to drug resistance and poor therapeutic outcomes especially for radiotherapy. Here we propose an in situ catalytic oxygenation strategy in tumor using porphyrinic metal-organic framework (MOF)-gold nanoparticles (AuNPs) nanohybrid as a therapeutic platform to achieve O₂ -evolving chemoradiotherapy. The AuNPs decorated on the surface of MOF effectively stabilize the nanocomposite and serve as radiosensitizers, whereas the MOF scaffold acts as a container to encapsulate chemotherapeutic drug doxorubicin. In vitro and in vivo studies verify that the catalase-like nanohybrid significantly enhances the radiotherapy effect, alleviating tumor hypoxia and achieving synergistic anticancer efficacy. This hybrid nanomaterial remarkably suppresses the tumor growth with minimized systemic toxicity, opening new horizons for the next generation of theranostic nanomedicines.

Keywords: catalase-like activity; chemoradiation therapy; controlled drug release; radiosensitizer; tumour hypoxia.

Figure 1.

Schematic representation showing the main components of Dox@MOF-Au-PEG and the mechanism of O₂ self-supplying synergistic chemoradiotherapy.

Figure 2.

a) TEM images and b) EDS mapping of MOF-Au NPs. c) O₂ generation by various samples with normalized MOF weight (1 mg mL⁻¹) in the presence of H₂O₂ at a physiological concentration of 400 μM. d) Release profiles of the porphyrin ligand under different conditions. Insets: TEM images of MOF-Au-PEG after incubation with water or PBS for 24 h.

Figure 3.

a) Bio-TEM images of U87MG cells after treatment with MOF-Au-PEG for 24 h. Arrows: purplish red, lysosomes; white, intact NPs with massive coating of small dark spots (AuNPs); blue, collapsed NPs manifested fewer decorations of AuNPs along with lighter contrast. b) CLSM images of U87MG cells treated with Dox@MOF-Au-PEG for different time. c) Cell survival rate and d) colon formation of U87MG cells after different treatments. Opposed to (−), (+) denotes X-ray was applied in the group. The concentration shown in c) and d) represents the normalized concentration of MOF.

Figure 4.

a) PET imaging of U87MG tumour-bearing mice at different time points p.i. of ⁶⁴Cu-MOF-Au-PEG. The green dashed circles represent the tumour locations. b) Quantitative ROI assay of major tissues (n = 3). c) HIF1-α immunofluorescence analysis of the tumour slices collected at 8 h p.i of saline or MOF-Au-PEG. d) Tumour growth curves of the mice administrated with different treatments (n = 5). e) The final relative tumour volume on day 13 after various treatments. *p < 0.05 vs. Dox@MOF-Au-PEG. **p < 0.01 vs. Dox@MOF-Au-PEG.