% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Philipp:603710,
      author       = {Philipp, Julian and Dabkowska, Aleksandra and Reiser, Anita
                      and Frank, Kilian and Krzysztoń, Rafał and Brummer,
                      Christiane and Nickel, Bert and Blanchet, Clement E. and
                      Sudarsan, Akhil and Ibrahim, Mohd and Johansson, Svante and
                      Skantze, Pia and Skantze, Urban and Östman, Sofia and
                      Johansson, Marie and Henderson, Neil and Elvevold, Kjetil
                      and Smedsrød, Bård and Schwierz, Nadine and Lindfors,
                      Lennart and Rädler, Joachim O.},
      title        = {p{H}-dependent structural transitions in cationic ionizable
                      lipid mesophases are critical for lipid nanoparticle
                      function},
      journal      = {Proceedings of the National Academy of Sciences of the
                      United States of America},
      volume       = {120},
      number       = {50},
      issn         = {0027-8424},
      address      = {Washington, DC},
      publisher    = {National Acad. of Sciences},
      reportid     = {PUBDB-2024-00898},
      pages        = {e2310491120},
      year         = {2023},
      abstract     = {Lipid nanoparticles (LNPs) are advanced core-shell
                      particles for messenger RNA (mRNA) based therapies that are
                      made of polyethylene glycol (PEG) lipid,
                      distearoylphosphatidylcholine (DSPC), cationic ionizable
                      lipid (CIL), cholesterol (chol), and mRNA. Yet the mechanism
                      of pH-dependent response that is believed to cause endosomal
                      release of LNPs is not well understood. Here, we show that
                      eGFP (enhanced green fluorescent protein) protein expression
                      in the mouse liver mediated by the ionizable lipids
                      DLin-MC3-DMA (MC3), DLin-KC2-DMA (KC2), and DLinDMA (DD)
                      ranks MC3 ≥ KC2 > DD despite similar delivery of mRNA per
                      cell in all cell fractions isolated. We hypothesize that the
                      three CIL-LNPs react differently to pH changes and hence
                      study the structure of CIL/chol bulk phases in water. Using
                      synchrotron X-ray scattering a sequence of ordered CIL/chol
                      mesophases with lowering pH values are observed. These
                      phases show isotropic inverse micellar, cubic Fd3m inverse
                      micellar, inverse hexagonal and bicontinuous cubic Pn3m
                      symmetry. If polyadenylic acid, as mRNA surrogate, is added
                      to CIL/chol, excess lipid coexists with a condensed nucleic
                      acid lipidphase. The next-neighbor distance in the excess
                      phase shows a discontinuity at the Fd3m inverse micellar to
                      inverse hexagonal transition occurring at pH 6 with
                      distinctly larger spacing and hydration for DD vs. MC3 and
                      KC2. In mRNA LNPs, DD showed larger internal spacing, as
                      well as retarded onset and reduced level of DD-LNP-mediated
                      eGFP expression in vitro compared to MC3 and KC2. Our data
                      suggest that the pH-driven Fd3m- transition in bulk phases
                      is a hallmark of CIL-specific differences in mRNA LNP
                      efficacy.},
      cin          = {EMBL-User / EMBL},
      ddc          = {500},
      cid          = {I:(DE-H253)EMBL-User-20120814 / I:(DE-H253)EMBL-20120731},
      pnm          = {6G3 - PETRA III (DESY) (POF4-6G3)},
      pid          = {G:(DE-HGF)POF4-6G3},
      experiment   = {EXP:(DE-H253)P-P12-20150101},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:38055742},
      UT           = {WOS:001498765900001},
      doi          = {10.1073/pnas.2310491120},
      url          = {https://bib-pubdb1.desy.de/record/603710},
}