Synergistic anticancer activity of Sulphoraphane and Teriflunomide co loaded lignin nanoparticles against triple negative breast cancer: Targeted nanoparticle delivery and drug repurposing

Abstract

Triple negative breast cancer stands out as the most aggressive subtype within the spectrum of breast malignancies, characterized by increased risks of recurrence, metastasis, and dismal prognosis. Notably, TNBC cells exhibit extensive overexpression of folate receptors, particularly folate receptor alpha, which drives tumor cell proliferation and migration. Addressing TNBC remains a formidable challenge in oncology, necessitating innovative therapeutic strategies. While chemotherapy serves as the cornerstone of TNBC treatment, its efficacy is often compromised by systemic toxicity, resulting in suboptimal clinical outcomes. This hypothesis proposes a novel approach utilizing lignin nanoparticles functionalized with folic acid for targeted delivery to FRα-overexpressing TNBC cells. These nanoparticles will encapsulate both the chemopreventive agent Sulphoraphane and the chemotherapeutic agent Teriflunomide, offering advantages such as enhanced drug targeting, synergistic therapeutic effects, cost-effectiveness, and reduced off-target toxicity. Additionally, this hypothesis highlights the repurposing of Teriflunomide to overcome drug resistance and the antioxidant properties of lignin. Furthermore, the ease of nanoparticle fabrication via self-assembly presents a promising avenue for streamlined production and clinical translation.