Synthesis and Optimization of the Docetaxel-Loaded and Durvalumab-Targeted Human Serum Albumin Nanoparticles, In Vitro Characterization on Triple-Negative Breast Cancer Cells

Abstract

Triple-negative breast cancer (TNBC) tends to behave more aggressively compared to other breast cancer subtypes due to the lack of receptors and its limited targeting therapy. In recent years, nanotechnology advancement has led to the development of various nanoparticle platforms for the targeted treatment of cancers. Especially, HSA-NPs have specific advantages such as biocompatibility, adjustable size during production, and relatively easy synthesis. In this study, HSA-NPs were encapsulated with docetaxel (DTX) and functionalized with polyethylene glycol (PEG), also becoming a targeting nanoplatform modified with durvalumab (DVL), and the whole nanostructure was well characterized. Subsequently, drug release studies and various in vitro cell culture studies such as determining the cytotoxicity and apoptotic levels of the nanoplatforms and PD-L1 using ELISA test were conducted on MDA-MB-468, MDA-MB-231, and MCF-7 cells. According to the results, HSA-DTX@PEG-DVL NPs showed better cytotoxicity compared to DTX in all the three cell lines. In addition, it was observed that the HSA-DTX@PEG-DVL NPs did not lead the cells to late apoptosis but were effective in the early apoptotic stage. Moreover, the ELISA data showed a significantly induced PD-L1 expression due to the presence of DVL in the nanostructure, which indicates that DVL antibodies successfully bind to the HSA-DTX@PEG-DVL nanostructure.