Combating Breast Cancer-associated Metastasis using Paclitaxel and Tranilast-loaded Human Serum Albumin Nanoparticles

The objective of the current study is to combat breast cancer-associated metastasis using paclitaxel (PTX) and tranilast (TRA)-loaded human serum albumin (HAS) Nanoparticles. This combinatorial therapy using microtubule stabilizing agent PTX, along with TGFβ inhibitor TRA.TRA may offer an improved therapeutic effect in breast cancer by inhibiting cell proliferation and metastasis. Inspired by the remarkable anticancer properties of both drugs, they were encapsulated into HSA nanoparticles to enhance tumor site-specific drug accumulation and ensure sustained release over a prolonged period. The HSA nanoparticles were fabricated using the desolvation method and optimized using a Box-Behnken design (BBD) with a three-level, two-factor approach. Further, these nanoparticles were characterized using TEM, FTIR, XRD, and particle size. <i>In vitro</i> experiments were conducted using the MDA-MB-231 cell line, employing cell viability, cellular uptake, nuclear staining, scratch assay, and cell cycle analysis. <i>In vitro</i> release kinetics reveal sustained PTX and TRA release from HSA nanoparticles. Wound healing assay depicted improved anti-migratory activity of PTX-TRA-NPs (30nM-75μM). Furthermore, the novel combination treatment caused G2/M phase cell cycle arrest, as indicated by cell cycle analysis HSA nanoparticles enhance the delivery and accumulation of hydrophobic drugs (PTX and TRA) in breast cancer cells, offering improved therapeutic outcomes. This combinatorial strategy permits further preclinical investigation for synergistic breast cancer management.