Drug-free Immunotherapeutic Biomimetic Nanoparticles for Treating Triple-Negative Breast Cancer

TL;DR

Researchers developed drug-free biomimetic nanoparticles that reduce tumor-associated macrophages and inhibit tumor growth in triple-negative breast cancer.

Contribution

Introduces MPsomes, macrophage biomimetic nanoparticles that modulate the tumor microenvironment without using drugs.

Findings

MPsomes reduced intratumoral TAMs populations and inhibited tumor growth in vivo.

MPsomes showed therapeutic efficacy comparable to FDA-approved anti-PD1 immunotherapy.

MPsomes selectively adhered to inflamed endothelium and reduced macrophage recruitment in vitro.

Abstract

Tumor-associated macrophages (TAMs) are key drivers of
tumor progression,
metastasis, and immune evasion in triple-negative breast cancer (TNBC).
Yet, most treatment strategies focus solely on tumor cells, neglecting
the immunosuppressive tumor microenvironment (TME). Given the strong
correlation between TAMs infiltration and poor prognosis, innovative
therapeutic strategies that modulate TAMs dynamics are urgently needed.
Here, we introduce MPsomes, macrophage biomimetic nanoparticles engineered
to disrupt TAMs recruitment and alter the TME. Fabricated via a microfluidic
approach, MPsomes integrate macrophage membrane proteins into lipid-based
nanoparticles, retaining key surface markers essential for immune
interactions. In vitro, MPsomes exhibited selective
adhesion to inflamed endothelium, reducing macrophage recruitment
in a flow chamber and Transwell migration assays. In vivo, systemic administration of MPsomes significantly reduced intratumoral
TAMs populations and resulted in a pronounced inhibition of tumor
growth compared to conventional liposomes. Notably, the therapeutic
efficacy of MPsomes was comparable to that of FDA-approved anti-PD1
immunotherapy, further underscoring their potential as a drug-free,
biomimetic alternative for TNBC treatment. These findings highlight
the potential of MPsomes as a drug-free immunotherapeutic platform
capable of reshaping the TME and inhibiting tumor progression, representing
a previously unexplored therapeutic approach for TNBC.

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