Aptamer targeted red blood cell membrane-coated porphyrinic copper-based MOF for guided photochemotherapy against metastatic breast cancer

Abstract Nanoscale porphyrinic metal−organic frameworks have emerged as promising therapeutic system for photodynamic therapy (PDT) of cancer in recent years. Nevertheless, their low selectivity towards malignant tissues is a hindrance for highly efficient cancer photodynamic therapy. In this study, a nano metal-organic framework ([CuL-[AlOH]2]n (Cu MOF), with Cu (II) core, as a PDT active center, was coated with red blood cell (RBC) membrane after loaded with doxorubicin (DOX), to avoid immediate clearance from the bloodstream and persist for longer periods of time in circulation. Then, a carboxylic acid-end aptamer (MUC1) was decorated on the RBC-coated DOX-loaded MOF (Apt-RBC-MOF@DOX) in order to provide targeted chemo and photodynamic therapy. The MTT and flow cytometry experiments exhibited that Apt-RBC-MOF@DOX provided highly efficient DOX transportation and toxicity against 4T1 and MCF7 breast cancer cells in vitro in comparison to non-targeted RBC-MOF@DOX. On the other hand, the single dose intravenous injection of Apt-RBC-MOF@DOX considerably reduced the tumor growth in vivo. The desirable biodistribution, faster liver clearance, and higher tumor accumulation were confirmed by ex vivo fluorescent imaging. Moreover, under irradiation at 630 nm, the fabricated nanostructures exhibited effective synergistic chemo and photodynamic therapy, proved via in vitro MTT assay and tumor ablation in vivo. The developed Apt-RBC-MOF@DOX could serve as a potent platform in clinic for targeted chemo-photodynamic dual therapy.