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@ARTICLE{Sebastiani:892285,
      author       = {Sebastiani, Federica and Yanez Arteta, Marianna and Lerche,
                      Michael and Porcar, Lionel and Lang, Christian and Bragg,
                      Ryan A. and Elmore, Charles S. and Krishnamurthy, Venkata R.
                      and Russell, Robert A. and Darwish, Tamim and Pichler,
                      Harald and Waldie, Sarah and Moulin, Martine and Haertlein,
                      Michael and Forsyth, V. Trevor and Lindfors, Lennart and
                      Cárdenas, Marité},
      title        = {{A}polipoprotein {E} {B}inding {D}rives {S}tructural and
                      {C}ompositional {R}earrangement of m{RNA}-{C}ontaining
                      {L}ipid {N}anoparticles},
      journal      = {ACS nano},
      volume       = {15},
      number       = {4},
      issn         = {1936-086X},
      address      = {Washington, DC},
      publisher    = {Soc.},
      reportid     = {FZJ-2021-01995},
      pages        = {6709 - 6722},
      year         = {2021},
      abstract     = {Emerging therapeutic treatments based on the production of
                      proteins by delivering mRNA have become increasingly
                      important in recent times. While lipid nanoparticles (LNPs)
                      are approved vehicles for small interfering RNA delivery,
                      there are still challenges to use this formulation for mRNA
                      delivery. LNPs are typically a mixture of a cationic lipid,
                      distearoylphosphatidylcholine (DSPC), cholesterol, and a
                      PEG-lipid. The structural characterization of
                      mRNA-containing LNPs (mRNA-LNPs) is crucial for a full
                      understanding of the way in which they function, but this
                      information alone is not enough to predict their fate upon
                      entering the bloodstream. The biodistribution and cellular
                      uptake of LNPs are affected by their surface composition as
                      well as by the extracellular proteins present at the site of
                      LNP administration, e.g., apolipoproteinE (ApoE). ApoE,
                      being responsible for fat transport in the body, plays a key
                      role in the LNP’s plasma circulation time. In this work,
                      we use small-angle neutron scattering, together with
                      selective lipid, cholesterol, and solvent deuteration, to
                      elucidate the structure of the LNP and the distribution of
                      the lipid components in the absence and the presence of
                      ApoE. While DSPC and cholesterol are found to be enriched at
                      the surface of the LNPs in buffer, binding of ApoE induces a
                      redistribution of the lipids at the shell and the core,
                      which also impacts the LNP internal structure, causing
                      release of mRNA. The rearrangement of LNP components upon
                      ApoE incubation is discussed in terms of potential relevance
                      to LNP endosomal escape.},
      cin          = {JCNS-FRM-II / MLZ / JCNS-1 / JCNS-4},
      ddc          = {540},
      cid          = {I:(DE-Juel1)JCNS-FRM-II-20110218 / I:(DE-588b)4597118-3 /
                      I:(DE-Juel1)JCNS-1-20110106 / I:(DE-Juel1)JCNS-4-20201012},
      pnm          = {6G4 - Jülich Centre for Neutron Research (JCNS) (FZJ)
                      (POF4-6G4) / 632 - Materials – Quantum, Complex and
                      Functional Materials (POF4-632)},
      pid          = {G:(DE-HGF)POF4-6G4 / G:(DE-HGF)POF4-632},
      experiment   = {EXP:(DE-MLZ)KWS2-20140101},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {33754708},
      UT           = {WOS:000645436800066},
      doi          = {10.1021/acsnano.0c10064},
      url          = {https://juser.fz-juelich.de/record/892285},
}