Lipid Cross-Linking of Nanolipoprotein Particles Substantially Enhances Serum Stability and Cellular Uptake

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

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)20549-20557
Number of pages9
JournalACS Applied Materials and Interfaces
Issue number32
StatePublished - Aug 17 2016


  • cross-linking
  • DiynePC
  • drug delivery
  • nanoparticles
  • NLP
  • rHDL
  • serum stability

ASJC Scopus subject areas

  • Materials Science(all)


Dive into the research topics of 'Lipid Cross-Linking of Nanolipoprotein Particles Substantially Enhances Serum Stability and Cellular Uptake'. Together they form a unique fingerprint.

Cite this