Ultra-dispersed biomimetic nanoplatform fabricated by controlled etching agglomerated MnO2 for enhanced photodynamic therapy and immune activation

Hypoxia plays a pivotal role in malignant tumor invasion and metastasis, affecting tumor therapeutic effect and tumor immune microenvironment (TME). Previous studies have proved that manganese dioxide (MnO2) nanoparticles could significantly improve the hypoxic tumor microenvironment. Yet the fatal disadvantage of agglomeration upon collection by centrifugation or other treatments limit their uses in hypoxia therapies. In this study, we avoided the agglomeration of MnO2 by a controlled etching method via the unique weak acidity of PEG-PLGA aqueous solution. Then, the photosensitizer chlorin e6 (Ce6) was loaded into the PEG-PLGA core and 4T1 cancer cell membrane fragments acting as a shell (PLGA-Ce6-MnO2@4T1M, [email protected]). After intravenous injection into the 4T1-tumor bearing mice, [email protected] showed homogeneous targeting to 4T1 tumor and greatly enhanced the effect of photodynamic therapy (PDT) in vivo. In addition, [email protected] also alleviate tumor hypoxia and polarize macrophages in the TME. More interestingly, [email protected] activated T-cells and maturated dendritic cells in vivo upon laser irradiation. All data showed that [email protected] can reshape the immunosuppressive TME and be promising in cancer treatment.