MnO2@Ce6 loaded mesenchymal stem cells as “oxygen-laden guided-missile” for enhanced photodynamic therapy on lung cancer

The critical issue in nanoscale medicine delivery system is the targeted efficiency to guarantee the maximum accumulation of nanodrug in tumor for better exerting therapeutic action. In this design, we adopted an active and potent strategy based on mesenchymal stem cells (MSCs) certified with excellent tumor-tropism ability to load and ship MnO2@Ce6 nanoparticles into tumor site. Notably, under the premise of negligible cellular toxicity of MnO2@Ce6 on MSCs, its considerable uptake by MSCs enabled this nanoplatform (MnO2@Ce6-MSCs) to distribute inside tumor increasingly. Briefly, Ce6 photosensitizer was bound to MnO2 nanospheres by physical adsorption, improving its own stability in blood circulation. Furthermore, the delivered MnO2@Ce6 could modulate tumor microenvironment (TME) by high sensitivity to excess hydrogen protons (H+) and H2O2. Thus, the O2 generated by these reactions served as abundant source for 1O2 conversion under 633 nm laser exposure, which overcame the crucial bottle-neck of the unfavorable hypoxia condition in TME for photodynamic therapy (PDT). Meanwhile, MnO2 decomposed into Mn2+, which represented high T1 relaxivity in magnetic resonance imaging (MRI) and finally was removed rapidly from the body by liver metabolism and kidney filtration. These results endowed the original nanoplatform with striking potentials for MSCs-guided, Ce6-converted, MRI-monitored PDT for further innovation of clinical cancer diagnosis-treatment agent.