title: Lipid Cross-Linking of Nanolipoprotein Particles Substantially Enhances Serum Stability and Cellular Uptake.
abstract: Nanolipoprotein particles (NLPs) consist of a discoidal phospholipid lipid bilayer confined by an apolipoprotein belt. NLPs are a promising platform for a variety of biomedical applications due to their biocompatibility, size, definable composition, and amphipathic characteristics. However, poor serum stability hampers the use of NLPs for in vivo applications such as drug formulation. In this study, NLP stability was enhanced upon the incorporation and subsequent UV-mediated intermolecular cross-linking of photoactive DiynePC phospholipids in the lipid bilayer, forming cross-linked nanoparticles (X-NLPs). Both the concentration of DiynePC in the bilayer and UV exposure time significantly affected the resulting X-NLP stability in 100% serum, as assessed by size exclusion chromatography (SEC) of fluorescently labeled particles. Cross-linking did not significantly impact the size of X-NLPs as determined by dynamic light scattering and SEC. X-NLPs had essentially no degradation over 48 h in 100% serum, which is a drastic improvement compared to non-cross-linked NLPs (50% degradation by ∼10 min). X-NLPs had greater uptake into the human ATCC 5637 bladder cancer cell line compared to non-cross-linked particles, indicating their potential utility for targeted drug delivery. X-NLPs also exhibited enhanced stability following intravenous administration in mice. These results collectively support the potential utility of X-NLPs for a variety of in vivo applications.
authors.affiliation: Biosciences and Biotechnology Division, Lawrence Livermore National Laboratory , Livermore, California 94551, United States.
authors.forename: Sean F
authors.initials: SF
authors.lastname: Gilmore
authors.affiliation: Biosciences and Biotechnology Division, Lawrence Livermore National Laboratory , Livermore, California 94551, United States.
authors.forename: Craig D
authors.initials: CD
authors.lastname: Blanchette
authors.affiliation: Department of Internal Medicine, Division of Hematology and Oncology, University of California-Davis (UC Davis) and UC Davis Comprehensive Cancer Center , 4501 X Street, Room 3016, Sacramento, California 95817, United States.
authors.forename: Tiffany M
authors.initials: TM
authors.lastname: Scharadin
authors.affiliation: Life Science Division, Lawrence Berkeley National Laboratory , Berkeley, California 94720, United States.|Chemistry and Biochemistry, University of California-Santa Cruz , Santa Cruz, California 95064, United States.
authors.forename: Greg L
authors.initials: GL
authors.lastname: Hura
authors.affiliation: Biosciences and Biotechnology Division, Lawrence Livermore National Laboratory , Livermore, California 94551, United States.
authors.forename: Amy
authors.initials: A
authors.lastname: Rasley
authors.affiliation: Biosciences and Biotechnology Division, Lawrence Livermore National Laboratory , Livermore, California 94551, United States.
authors.forename: Michele
authors.initials: M
authors.lastname: Corzett
authors.affiliation: Department of Internal Medicine, Division of Hematology and Oncology, University of California-Davis (UC Davis) and UC Davis Comprehensive Cancer Center , 4501 X Street, Room 3016, Sacramento, California 95817, United States.
authors.forename: Chong-Xian
authors.initials: CX
authors.lastname: Pan
authors.affiliation: Biosciences and Biotechnology Division, Lawrence Livermore National Laboratory , Livermore, California 94551, United States.
authors.forename: Nicholas O
authors.initials: NO
authors.lastname: Fischer
authors.affiliation: Department of Internal Medicine, Division of Hematology and Oncology, University of California-Davis (UC Davis) and UC Davis Comprehensive Cancer Center , 4501 X Street, Room 3016, Sacramento, California 95817, United States.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Henderson
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002850:Chromatography, Gel; D006801:Humans; D008051:Lipid Bilayers; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D010743:Phospholipids
chemical_list: D008051:Lipid Bilayers; D010743:Phospholipids
keywords: DiynePC; NLP; cross-linking; drug delivery; nanoparticles; rHDL; serum stability