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

Abstract

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