Platelet membrane biomimetic bufalin-loaded hollow MnO₂ nanoparticles for MRI-guided chemo-chemodynamic combined therapy of cancer

In this study, platelet membrane (PLTM) biomimetic hollow MnO₂ nanoparticles were prepared and these were investigated for delivery of bufalin. Additionally, these nanoparticles, in response to the tumor microenvironment, showed rapid drug release and generated the hydroxyl radicals (HO•) by the Fenton reaction between Mn²⁺ and endogenous H₂O₂ for use in MRI-guided anti-tumor activity. Firstly, poly(lactic-co-glycolic acid) (PLGA) nanoparticles were used to reduce KMnO₄ to HMnO₂ nanoparticles followed by acetone etching. After bufalin loading, these NPs were biomimetically cloaked with PLTM to form PLTM-HMnO2@Bu NPs. In vitro release profiles showed that the NPs responded to acid pH and glutathione (GSH) to induce decomposition of MnO2, resulting in rapid release of bufalin and yielding the MRI contrast agent Mn²⁺. In vivo MRI studies revealed an obvious T1 contrast enhancement at the tumor site because of a combination of the EPR and active targeting effects. The PLTM-HMnO₂ NPs led to effective inhibition of tumor growth, attributing to Fenton-like Mn²⁺ conversion of endogenous H₂O₂ in the tumor to highly toxic HO• and this anti-tumor efficacy was enhanced when combined with chemotherapy. These results indicate that the PLTM biomimetic HMnO₂ nanoparticles are promising drug delivery systems for MRI-monitoring and enhanced targeted treatment of tumors.