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 center dot) 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.