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<p>Triple-negative breast cancer is an aggressive cancer with high metastatic potential and limited treatment options. The current study investigated the anticancer activity of the <i>Polybia</i>-derived MP-1 peptide, formulated in poly (lactic-co-glycolic acid) (PLGA) nanoparticles, for inhibiting PD-L1 and epithelial mesenchymal transition (EMT)-associated signalling in triple-negative breast cancer (TNBC). Computational screening of molecules identified MP-1 as a stable high-affinity binder of PD-L1 possessing high anticancer prediction scores. The MP-1-PLGA nanoparticles that were optimized showed the spherical structures with a size of 104.4&#xa0;nm as well as a PDI of 0.231. Moreover, their encapsulation efficiency was 71.5%. The formulation showed a controlled release with 41.65% over 72&#xa0;h (p &lt; 0.01). According to in vitro assays, the lower IC₅₀ value of MP-1-PLGA nanoparticles (19.39&#xa0;µg/mL) than free MP-1 (53.51&#xa0;µg/mL) confirmed enhanced cytotoxic activity. Gene expression studies showed significant down regulation of <i>PD-L1, EGFR, STAT3, BCL2</i> and <i>Ki-67</i>, while the up regulation of <i>Caspase-3, Caspase-9 and BAX</i> (p &lt; 0.0001). Western blot results verified reduced expression of PD-L1 and EGFR. The PLGA nanoparticles loaded with MP-1 targeted the PD-L1 effectively and modulated the Molecular Pathways related with EMT which inhibit tumor cell proliferation and enhance their apoptosis. The results indicate MP-1–PLGA as a potential nontherapeutic candidate for improving TNBC treatment.</p> Graphical abstract <p></p>

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PD-L1 targeting in triple negative breast cancer: in silico and in vitro validation of wasp venom peptide MP-1

  • 期刊论文

  • 发表日期：

    2025年11月24日

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  • Azra Sakhawat,
  • Muhammad Umer Khan,
  • Samiullah Khan,
  • Nadeem Ahmed,
  • Alaa S. Alhegaili,
  • Badriyah S. Alotaibi

摘要

Triple-negative breast cancer is an aggressive cancer with high metastatic potential and limited treatment options. The current study investigated the anticancer activity of the Polybia-derived MP-1 peptide, formulated in poly (lactic-co-glycolic acid) (PLGA) nanoparticles, for inhibiting PD-L1 and epithelial mesenchymal transition (EMT)-associated signalling in triple-negative breast cancer (TNBC). Computational screening of molecules identified MP-1 as a stable high-affinity binder of PD-L1 possessing high anticancer prediction scores. The MP-1-PLGA nanoparticles that were optimized showed the spherical structures with a size of 104.4 nm as well as a PDI of 0.231. Moreover, their encapsulation efficiency was 71.5%. The formulation showed a controlled release with 41.65% over 72 h (p < 0.01). According to in vitro assays, the lower IC₅₀ value of MP-1-PLGA nanoparticles (19.39 µg/mL) than free MP-1 (53.51 µg/mL) confirmed enhanced cytotoxic activity. Gene expression studies showed significant down regulation of PD-L1, EGFR, STAT3, BCL2 and Ki-67, while the up regulation of Caspase-3, Caspase-9 and BAX (p < 0.0001). Western blot results verified reduced expression of PD-L1 and EGFR. The PLGA nanoparticles loaded with MP-1 targeted the PD-L1 effectively and modulated the Molecular Pathways related with EMT which inhibit tumor cell proliferation and enhance their apoptosis. The results indicate MP-1–PLGA as a potential nontherapeutic candidate for improving TNBC treatment.

Graphical abstract