Synthesis of thermoresponsive nanostructured lipid carrier core with poly(N-isopropylacrylamide) shell nanoparticle for drug encapsulation and intraductal delivery into the mammary tissue

Abstract

Breast cancer have a high incidence worldwide, but there is a lack of effective and well-accepted alternatives for localized treatment of noninvasive forms of the disease, such as ductal carcinoma in situ (DCIS). In this project, we propose the development of nanocarriers for intraductal drug administration, aiming to optimize the drug localization in the breast tissue, improving efficacy and reducing systemic adverse effects. More specifically, we propose the encapsulation of nanostructured lipid carriers containing the cytotoxic drug paclitaxel within a shell of poly(N-isopropylacrylamide) (pNIPAM), a thermoresponsible polymer that allows drug controlled release. The pNIPAM shell will also be functionalized with SILY, a peptide that binds to collagen type I, which is overexpressed in the tumor microenvironment of several types of cancer, including breast cancer. The nanoparticles will be characterized for size, polydispersity index, zeta potential and drug loading. Paclitaxel release and nanoparticle-collagen binding will be assessed in vitro. The mechanisms of uptake of these nanoparticles into T47D cells (a breast cancer cell line) will be investigated via live cell imaging using confocal microscopy. With this study, we aim to contribute to the development of a safer and effective platform for the treatment of DCIS. (AU)