Nanoparticles (NPs) use for drug delivery or vaccines is highly successful. Given this, optimizing a NP's biological identity for maximal therapeutic benefit remains challenging. Macromolecules absorption from biofluids by NPs forms a layer called the protein corona. Herein, we examined a corona's influence on the uptake of polymeric NPs, made with a hyperbranched polyester polymer (HBPE), by breast cancer cells. Moreover, a corona's ability to increase cancer killing through improved paclitaxel (taxol) drug delivery was evaluated. Normal and influenza A virus (IAV)-infected mice sera were employed as coronal protein sources. Pre-coating NPs with sera may enrich NP surfaces with proteins that favor cancer interaction. In turn, a NP's ability to reach tumors may be enhanced by exploiting normal or IAV sera content. For normal and IAV sera studies, polyethylene glycol (PEG), a gold-standard NP surface modification for in vivo delivery, served as a control to sera-incubated HBPE-NPs. Sera pre-coated HBPE-NPs exhibited enhanced breast cancer cell uptake and tumor localization, over PEGylated HBPE-NPs. Additionally, breast cancer treatment with sera pre-coated HBPE-NPs resulted in greater taxol-mediated killing compared to PEGylated HBPE-NP treatment. Sera pre-coated HBPE-NPs additionally demonstrated greater uptake in cancer cells in an in vitro transwell system. The transwell system involved NP treatment in an upper chamber containing endothelial cells and assaying NP uptake in a lower chamber containing cancer cells. IAV sera coating enhanced NP localization to breast cancer tumors, while lowering liver and spleen accumulation in mice. We show HBPE-NPs incubation with normal and immune response-derived IAV sera can form coronas with unique proteins. Our findings suggest that sera collected during an immune response to infection are a rich source of coronal proteins that could form the basis of a preformed protein corona that ensures the optimal biological identify for targeted cancer cell uptake as described herein.
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Doctor of Philosophy (Ph.D.)
College of Medicine
Burnett School of Biomedical Sciences
Length of Campus-only Access
Doctoral Dissertation (Campus-only Access)
College of Medicine
Nierenberg, Daniel, "Utilization of HBPE Nanoparticles for Optimizing Drug Delivery to Cancer Cells" (2021). Electronic Theses and Dissertations, 2020-. 739.