Lipid cross-linking of nanolipoprotein particles substantially enhances serum stability and cellular uptake [Lipid crosslinking enhances the stability of nanolipoprotein particles in serum by multiple orders of magnitude]

Gilmore, Sean F.; Blanchette, Craig D.; Scharadin, Tiffany M.; Hura, Greg L.; Rasley, Amy; Corzett, Michele; Pan, Chong-xian; Fischer, Nicholas O.; Henderson, Paul T.

doi:10.1021/acsami.6b04609

Lipid cross-linking of nanolipoprotein particles substantially enhances serum stability and cellular uptake [Lipid crosslinking enhances the stability of nanolipoprotein particles in serum by multiple orders of magnitude]

Journal Article · Wed Jul 13 00:00:00 EDT 2016 · ACS Applied Materials and Interfaces

DOI:https://doi.org/10.1021/acsami.6b04609· OSTI ID:1342026

Gilmore, Sean F. ^[1]; Blanchette, Craig D. ^[1]; Scharadin, Tiffany M. ^[2]; Hura, Greg L. ^[3]; Rasley, Amy ^[1]; Corzett, Michele ^[1]; Pan, Chong-xian ^[2]; Fischer, Nicholas O. ^[1]; Henderson, Paul T. ^[2]

Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Biosciences and Biotechnology Division
Univ. of California, Davis, CA (United States). UC Davis Comprehensive Cancer Center, Dept. of Internal Medicine and Division of Hematology and Oncology
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Science Division; Univ. of California, Santa Cruz, CA (United States). Dept. of Chemistry and Biochemistry

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. Lastly, these results collectively support the potential utility of X-NLPs for a variety of in vivo applications.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States); Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)

Sponsoring Organization:: National Inst. of Health (NIH); USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)

Grant/Contract Number:: AC02-05CH11231; AC52-07NA27344

OSTI ID:: 1342026

Alternate ID(s):: OSTI ID: 1440936

Report Number(s):: LLNL-JRNL--683565

Journal Information:: ACS Applied Materials and Interfaces, Journal Name: ACS Applied Materials and Interfaces Journal Issue: 32 Vol. 8; ISSN 1944-8244

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
DiynePC
NLP
cross-linking
drug delivery
nanoparticles
rHDL
serum stability

Lipid cross-linking of nanolipoprotein particles substantially enhances serum stability and cellular uptake [Lipid crosslinking enhances the stability of nanolipoprotein particles in serum by multiple orders of magnitude]

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References (50)

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