Dual-response oxygen-generating MnO2 nanoparticles with polydopamine modification for combined photothermal-photodynamic therapy

Photonic therapy (e.g., photodynamic therapy (PDT) and photothermal therapy (PTT)), features easy handling, good targeting, high curative effect and lower side effects compared to other treatments, thus showing considerable potential in cancer treatment. However, adverse tumor microenvironment, low light conversion efficiency, and inherent toxicity of photonic agents limit their further application in clinic. In this work, hollow mesoporous MnO2 nanoparticles (NPs) loaded with photosensitizer chlorin e6 and coated with folic acid-functionalized polydopamine were fabricated, and used as a platform for photonic therapy. The NPs enabled accurately controlled drug release, and sustainable and extensive O2 production by reacting with endogenous H2O2 in vitro. In addition, the NPs allowed efficient NIR light-to-heat conversion, owing to the core-shell MnO2/polydopamine structure. With the synergy of folic acid mediated active targeting and enhanced permeability and retention effect mediated passive targeting, a pronounced NPs accumulation at the tumor sites of mouse model was observed. The NPs also exhibited excellent biodegradation properties, alleviating the possible concerns about the long-term safety of photonic agents. Finally, a combination of O2-strengthened PDT and PTT resulted in effective tumor growth inhibition upon irradiation with 660 nm and 808 nm laser in vivo treatment. The above features of the devised NPs highlight their potential for improved cancer therapy and imaging.