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

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. <i>In vitro</i>, MPsomes exhibited selective adhesion to inflamed endothelium, reducing macrophage recruitment in a flow chamber and Transwell migration assays. <i>In vivo</i>, 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.