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Perfluorohexane Emulsions Induce Macrophage-Stimulating Effects through iNOS Expression.

Ruoqi Gao1, Ethan Wang1, Victor Pineiro1

  • 1Department of Radiology, Translational Research in Ultrasound Theranostics (TRUST) Program, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States.

ACS Applied Bio Materials
|April 11, 2025
PubMed
Summary
This summary is machine-generated.

Perfluorohexane nanodroplets activate macrophages to express iNOS, enhancing cancer cell apoptosis and reducing tumor size in mice. Aspirating gas pockets formed by these nanodroplets negated the anti-tumor effects.

Keywords:
cancerimmunomodulationmacrophagenanomedicineperfluorohexane

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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Immunotherapy

Background:

  • Cancer immunotherapy efficacy is limited, necessitating novel therapeutic strategies.
  • Perfluorocarbon (PFC) particles are explored for macrophage imaging due to their unique properties and 19F-MRI traceability.
  • The impact of PFC particle uptake on macrophage behavior remains largely uncharacterized.

Purpose of the Study:

  • To investigate the effect of phospholipid-stabilized perfluorohexane (PFH) nanodroplets (NDs) on macrophage behavior and anti-tumor activity.
  • To assess the potential of PFH NDs as a theranostic platform for cancer treatment.

Main Methods:

  • Bone-marrow-derived macrophages (BMDMs) and a murine colon carcinoma model were treated with PFH NDs.
  • Physiological responses were evaluated using biochemistry, flow cytometry, fluorescence imaging, and tumor measurements.
  • Comparison with high-boiling-point perfluorooctyl bromide (PFOB) emulsions was performed.

Main Results:

  • PFH ND incubation increased inducible nitric oxide synthase (iNOS) expression in alternatively-activated (M2) BMDMs.
  • Co-culture with tumor cells enhanced PFH ND-induced iNOS expression, leading to increased tumor cell apoptosis.
  • Intratumoral PFH ND injection reduced tumor size, associated with peritumoral gas pocket formation; aspiration of these pockets abolished the effect.

Conclusions:

  • PFH nanodroplets exhibit immunogenic potential by upregulating iNOS expression in macrophages.
  • PFH NDs demonstrate anti-tumor effects in a murine colon carcinoma model.
  • The findings support the development of theranostic PFC-based platforms for cancer immunotherapy.