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Title: 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]

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 formore » a variety of in vivo applications.« less
 [1] ;  [1] ;  [2] ;  [3] ;  [1] ;  [1] ;  [2] ;  [1] ;  [2]
  1. Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Biosciences and Biotechnology Division
  2. Univ. of California, Davis, CA (United States). UC Davis Comprehensive Cancer Center, Dept. of Internal Medicine and Division of Hematology and Oncology
  3. 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
Publication Date:
Report Number(s):
Journal ID: ISSN 1944-8244; TRN: US1701786
Grant/Contract Number:
AC52-07NA27344; 15- LW-023; GM105404; NCI R01CA155642; AC02-05CH11231
Accepted Manuscript
Journal Name:
ACS Applied Materials and Interfaces
Additional Journal Information:
Journal Volume: 8; Journal Issue: 32; Journal ID: ISSN 1944-8244
American Chemical Society (ACS)
Research Org:
Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23); National Institutes of Health (NIH)
Country of Publication:
United States
59 BASIC BIOLOGICAL SCIENCES; cross-linking; DiynePC; drug delivery; nanoparticles; NLP; rHDL; serum stability
OSTI Identifier:
Alternate Identifier(s):
OSTI ID: 1440936