Trilayer Tubular Scaffold to Mimic Ductal Carcinoma Breast Cancer for the Study of Chemo-Photothermal Therapy

Abstract

Ductal carcinoma in situ (DCIS) is a type of breast cancer resulting from malignant epithelial cells, which can become aggressive and dangerous over time due to the accumulation of cells in ducts. Finding more fruitful therapeutic strategies is a current demand in the field, and developing tumor models is a crucial approach to providing a suitable platform to investigate therapeutic strategies. Herein, a trilayer tubular 3D scaffold was developed as a DCIS model to imitate a real complex tissue microenvironment for cancerous cell culturing and treatment by chemo-photothermal therapy. The fabricated trilayer tubular scaffold through the sequential electrospinning consists of PLA/PCL nanofibers as a middle layer surrounded by alginate-dopamine/PVA nanofibers as outer and inner layers. The middle layer gives dimensional and mechanical stability to the scaffold, and its hydrophobicity can be balanced by two surrounding hydrophilic outer and inner layers to provide a suitable microenvironment for cell growth. Furthermore, the electrospun nanofibrous scaffold can mimic and resemble the microstructure of natural extracellular matrix (ECM) architecture to enhance cell proliferation. Then, the inner and outer layers were decorated with polydopamine nanoparticles to introduce photothermal ability and to improve cell adhesion. MDA-MB-231 breast cancer cells were cultured on the scaffold, and in vitro assays disclosed that the cells grew and expanded well on the scaffold. Concomitant administration of docetaxel and laser irradiation on the cultured cells on the scaffold (chemo-photothermal therapy) unveiled a synergistic inhibitory effect on cancer cells. These capabilities make the 3D trilayer tubular scaffold a promising platform for drug discovery and screening studies.