Objective To prepare doxorubicin (Dox)-loaded hollow mesoporous manganese dioxide (H-MnO₂) nanoparticles encapsulated with pH-sensitive fusion membrane (MP) (MP@H-MnO₂-Dox nanoparticles), and investigate its characteristics in vitro.Methods With solid silica as template, H-MnO₂ was synthesized by alkali etching. Dox-loaded H-MnO₂ (H-MnO₂-Dox) was prepared and was coated with MP to construct MP@H-MnO₂-Dox nanoparticles. The particle size, drug loading and proportion of MP coating carriers were investigated, the oxygen production capacity was evaluated by tris(4, 7-diphenyl-1, 10-phenanthroline)ruthenium(Ⅱ) dichloride (RDPP) probe, the drug release in vitro was investigated by dialysis, and the celluar uptake and distribution were investigated by confocal laser scanning microscopy.Results H-MnO₂ was successfully prepared. The drug-loading rate and encapsulation efficiency were (79.0±8.7)% and (75.1±7.5)%, respectively. H-MnO₂ could be coated well with the mass ratio 1:1 of MP to H-MnO₂. The particle size of MP@H-MnO₂-Dox nanoparticles was (178.0±9.5) nm. The results of RDPP showed that H-MnO₂ possessed superior oxygen production capacity. In vitro drug release results showed that MP could delay Dox release, and the Dox cumulative release amount of MP@H-MnO₂-Dox (pH=6.5) was lower than that of H-MnO₂-DOX (pH=6.5) ([42.0±5.1]% vs[60.0±3.7]%). The results of uptake experiments showed that MP@H-MnO₂-Dox nanoparticles had strong cellular uptake at pH=6.5.Conclusion MP@H-MnO₂-Dox nanoparticle is successfully constructed. This biomimetic nanosystem is expected to be a multifunctional drug delivery vehicle for alleviating hypoxia and targeting breast cancer.