Combating breast cancer-associated metastasis using paclitaxel and tranilast-loaded human serum albumin nanoparticles
Naitik Jain, Syed Shahrukh, Paras Famta, Saurabh Shah, Ganesh Vambhurkar, Dadi A. Srinivasarao, Anamika Sharma, Giriraj Pandey, Suraj Wagh, Swapnil Shinde, Anjesh Khan, Prashanth Kumar, Saurabh Srivastava
Abstract
Objective The objective of the current study is to combat breast cancer-associated metastasis using paclitaxel (PTX) and tranilast (TRA)-loaded human serum albumin (HSA) nanoparticles.Significance This combinatorial therapy uses 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.Methods 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. In vitro experiments were conducted using the MDA-MB-231 cell line, employing cell viability, cellular uptake, nuclear staining, scratch assay, and cell cycle analysis.Key findings In vitro release kinetics reveal sustained PTX and TRA release from HSA nanoparticles. Wound healing assay depicted improved anti-migratory activity of PTX-TRA-NPs (30 nM to 75 µM). Furthermore, the novel combination treatment caused G2/M phase cell cycle arrest, as indicated by cell cycle analysis.Conclusion 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.