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MnO2/Ce6 microbubble-mediated hypoxia modulation for enhancing sono-photodynamic therapy against triple negative breast cancer.

Abstract
Sono-photodynamic therapy (SPDT) has emerged as a promising treatment modality for triple negative breast cancer (TNBC). However, the hypoxic tumor microenvironment hinders the application of SPDT. Herein, in this study, a multifunctional platform (MnO2/Ce6@MBs) was designed to address this issue. A sono-photosensitizer (Ce6) and a hypoxia modulator (MnO2) were loaded into microbubbles and precisely released within tumor tissues under ultrasound irradiation. MnO2in situ reacted with the excess H2O2 and H+ and produced O2 within the TNBC tumor, which alleviated hypoxia and augmented SPDT by increasing ROS generation. Meanwhile, the reaction product Mn2+ was able to achieve T1-weighted MRI for enhanced tumor imaging. Additionally, Ce6 and microbubbles served as a fluorescence imaging contrast agent and a contrast-enhanced ultrasound imaging agent, respectively. In in vivo anti-tumor studies, under the FL/US/MR imaging guidance, MnO2/Ce6@MBs combined with SPDT significantly reversed tumor hypoxia and inhibited tumor growth in 4T1-tumor bearing mice. This work presents a theragnostic system for reversing tumor hypoxia and enhancing TNBC treatment.
AuthorsPing Li, Xiao Tan, Qing Dan, Azhen Hu, Zhengming Hu, Xiaoting Yang, Jianhua Bai, Xiaoyu Chen, Bowei Li, Guanxun Cheng, Li Liu, Yun Chen, Desheng Sun, Xintao Shuai, Tingting Zheng
JournalBiomaterials science (Biomater Sci) Vol. 12 Issue 6 Pg. 1465-1476 (Mar 12 2024) ISSN: 2047-4849 [Electronic] England
PMID38318975 (Publication Type: Journal Article)
Chemical References
  • Manganese Compounds
  • Hydrogen Peroxide
  • Oxides
  • Photosensitizing Agents
  • Porphyrins
Topics
  • Humans
  • Animals
  • Mice
  • Triple Negative Breast Neoplasms (diagnostic imaging, drug therapy)
  • Microbubbles
  • Manganese Compounds
  • Hydrogen Peroxide
  • Cell Line, Tumor
  • Oxides
  • Photochemotherapy (methods)
  • Photosensitizing Agents (pharmacology, therapeutic use)
  • Hypoxia
  • Porphyrins (pharmacology)
  • Tumor Microenvironment

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