Nanolipoprotein particles (NLPs) are reconstituted high-density lipoproteins, consisting of a phospholipid bilayer stabilized by an apolipoprotein scaffold protein. This class of nanoparticle has been a vital tool in the study of membrane proteins, and in recent years has been increasingly used for in vivo applications. Previous work demonstrated that the composition of the lipid bilayer component affects the stability of these particles in serum solutions. In the current study, NLPs assembled with phosphatidylcholine lipids featuring different acyl chain structures were systematically tested to understand the effect that lipid composition has on NLP stability in both neat serum and cell culture media supplemented with 10% serum by volume. The time at which 50% of the particles dissociate, as well as the fraction of the initial population that remains resistant to dissociation, were correlated to key parameters obtained from all-atom simulations of the corresponding lipid bilayers. A significant correlation was observed between the compressibility modulus of the lipid bilayer and particle stability in these complex biological milieu. These results can be used as a reference to tune the stability of these versatile biological nanoparticles for in vitro and in vivo applications.
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http://dx.doi.org/10.1039/C7NR09690A | DOI Listing |
Nat Med
January 2025
Merkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Prion disease is a fatal neurodegenerative disease caused by the misfolding of prion protein (PrP) encoded by the PRNP gene. While there is currently no cure for the disease, depleting PrP in the brain is an established strategy to prevent or stall templated misfolding of PrP. Here we developed in vivo cytosine and adenine base strategies delivered by adeno-associated viruses to permanently modify the PRNP locus to achieve PrP knockdown in the mouse brain.
View Article and Find Full Text PDFNat Commun
January 2025
Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California San Diego, La Jolla, CA, USA.
Amidst the rising prevalence of respiratory diseases, the importance of effective lung treatment modalities is more critical than ever. However, current drug delivery systems face significant limitations that impede their efficacy and therapeutic outcome. Biohybrid microrobots have shown considerable promise for active in vivo drug delivery, especially for pulmonary applications via intratracheal routes.
View Article and Find Full Text PDFMed Phys
January 2025
Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, USA.
Purpose: In locations where the proton energy spectrum is broad, lineal energy spectrum-based proton biological effects models may be more accurate than dose-averaged linear energy transfer (LET) based models. However, the development of microdosimetric spectrum-based biological effects models is hampered by the extreme computational difficulty of calculating microdosimetric spectra. Given a precomputed library of lineal energy spectra for monoenergetic protons, a weighted summation can be performed which yields the lineal energy spectrum of an arbitrary polyenergetic beam.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
January 2025
East China Normal University, State Key Laboratory of Precision Spectroscopy, 500 Dongchuan Rd., 200241, Shanghai, CHINA.
Near-infrared (NIR) triplet dyes are the cornerstones of cutting-edge biomedical and material applications. The difficulty in rational development of triplet dyes increases exponentially as the absorption wavelength shifts deeper into the NIR range. Although classical H-/J-typed packing of NIR dyes has the potential to enhance intersystem crossing (ISC) compared with that in single-chromophore dyes, the triplet state quantum yields remain limited in such strategy.
View Article and Find Full Text PDFAnnu Rev Anal Chem (Palo Alto Calif)
January 2025
1Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio, USA; email:
The use of cell culture techniques to model human disease is an indispensable tool that has helped improve the health and well-being of the world. Monolayer cultures have most often been used for biomedical research, although not accurately recapitulating an in vivo human tumor. Tumor spheroids are a form of three-dimensional cell culture that better mimics an avascularized human tumor through their cell-cell contacts in all directions, development of various chemical gradients, and distinct populations of cells found within the spheroid.
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