Biomimetic liposomal nanozymes improve breast cancer chemotherapy with enhanced penetration and alleviated hypoxia

J Nanobiotechnology. 2023 Apr 10;21(1):123. doi: 10.1186/s12951-023-01874-7.

Abstract

Background: Doxorubicin (Dox) has been recommended in clinical guidelines for the standard-of-care treatment of breast cancer. However, Dox therapy faces challenges such as hypoxia, acidosis, H2O2-rich conditions and condensed extracellular matrix in TME as well as low targeted ability.

Methods: We developed a nanosystem H-MnO2-Dox-Col NPs based on mesoporous manganese dioxide (H-MnO2) in which Dox was loaded in the core and collagenase (Col) was wrapped in the surface. Further the H-MnO2-Dox-Col NPs were covered by a fusion membrane (MP) of inflammation-targeted RAW264.7 cell membrane and pH-sensitive liposomes to form biomimetic MP@H-MnO2-Dox-Col for in vitro and in vivo study.

Results: Our results shows that MP@H-MnO2-Dox-Col can increase the Dox effect with low cardiotoxicity based on multi-functions of effective penetration in tumor tissue, alleviating hypoxia in TME, pH sensitive drug release as well as targeted delivery of Dox.

Conclusions: This multifunctional biomimetic nanodelivery system exhibited antitumor efficacy in vivo and in vitro, thus having potential for the treatment of breast cancer.

Keywords: Biomimetic nanoparticles; Breast cancer; Chemotherapy; Hypoxia; Penetration.

MeSH terms

  • Biomimetics
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / pathology
  • Cell Line, Tumor
  • Doxorubicin
  • Female
  • Humans
  • Hydrogen Peroxide / metabolism
  • Hypoxia / drug therapy
  • Liposomes / therapeutic use
  • Manganese Compounds
  • Nanoparticles*
  • Oxides / therapeutic use

Substances

  • Liposomes
  • Manganese Compounds
  • Hydrogen Peroxide
  • Oxides
  • Doxorubicin