Biomimetic oxygen delivery nanoparticles for enhancing photodynamic therapy in triple-negative breast cancer

Hanyi Fang1,2, Yongkang Gai1,2, Sheng Wang3

  • 1Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Abstract

Insights

Triple-negative breast cancer (TNBC) is aggressive, but a new cancer cell membrane-coated nanoprobe (CCm-HSA-ICG-PFTBA) effectively targets tumors, reduces hypoxia, and enhances photodynamic therapy (PDT) efficacy, improving treatment outcomes.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cancer Therapy

Background:

  • Triple-negative breast cancer (TNBC) presents significant therapeutic challenges due to its aggressive nature, high metastatic potential, and resistance to conventional treatments.
  • Hypoxia within the tumor microenvironment exacerbates TNBC's aggressiveness and limits the effectiveness of therapies like photodynamic therapy (PDT).

Purpose of the Study:

  • To develop and evaluate a novel cancer cell membrane-coated oxygen delivery nanoprobe (CCm-HSA-ICG-PFTBA) for enhanced TNBC treatment.
  • To investigate the potential of this nanoprobe to alleviate tumor hypoxia and improve PDT efficacy in TNBC models.

Main Methods:

  • Fabrication of CCm-HSA-ICG-PFTBA nanoparticles (131.3 ± 1.08 nm) utilizing cancer cell membranes, human serum albumin (HSA), indocyanine green (ICG), and perfluorocarbon (PFTBA).
  • In vitro assessment of reactive oxygen species (ROS) generation and in vivo evaluation using fluorescence imaging, 18F-FMISO PET imaging, and immunofluorescence staining to confirm hypoxia mitigation.
  • In vivo efficacy studies involving photodynamic therapy (PDT) with near-infrared (NIR) laser irradiation on TNBC xenografts.

Main Results:

  • CCm-HSA-ICG-PFTBA significantly increased in vitro 1O2 and ROS concentrations compared to control groups.
  • In vivo imaging confirmed successful tumor targeting and significant reduction of tumor hypoxia 24 hours post-injection.
  • PDT treatment with CCm-HSA-ICG-PFTBA and NIR resulted in the smallest tumor volume and weight, demonstrating significant therapeutic effects with no observed biotoxicity.

Conclusions:

  • The CCm-HSA-ICG-PFTBA nanoprobe effectively targets tumors, combats hypoxia, and enhances PDT efficacy in TNBC models by leveraging cancer cell membrane properties and perfluorocarbon oxygen solubility.
  • The use of FDA-approved materials (HSA, ICG, PFC) ensures high biocompatibility, suggesting strong potential for clinical translation in treating TNBC patients.