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@ARTICLE{Carucci:626433,
      author       = {Carucci, Cristina and Philipp, Julian and Müller, Judith
                      A. and Sudarsan, Akhil and Kostyurina, Ekaterina and
                      Blanchet, Clement E. and Schwierz, Nadine and Parsons, Drew
                      F. and Salis, Andrea and Rädler, Joachim O.},
      title        = {{B}uffer {S}pecificity of {I}onizable {L}ipid
                      {N}anoparticle {T}ransfection {E}fficiency and {B}ulk
                      {P}hase {T}ransition},
      journal      = {ACS nano},
      volume       = {19},
      number       = {11},
      issn         = {1936-0851},
      address      = {Washington, DC},
      publisher    = {Soc.},
      reportid     = {PUBDB-2025-01412},
      pages        = {10829 - 10840},
      year         = {2025},
      note         = {Waiting for fulltext},
      abstract     = {Lipid nanoparticles (LNPs) are efficient and safe carriers
                      for mRNA vaccines based on advanced ionizable lipids. It is
                      understood that the pH-dependent structural transition of
                      the mesoscopic LNP core phase plays a key role in mRNA
                      transfer. However, buffer-specific variations in
                      transfection efficiency remain obscure. Here we analyze the
                      effect of the buffer type on the transfection efficiency of
                      LNPs. We find that LNPs formulated with the cationic
                      ionizable lipids DLin-MC3-DMA (MC3), SM-102, and ALC-315 in
                      citrate compared to phosphate and acetate buffers exhibit
                      earlier onset and stronger mRNA-GFP expression in vitro.
                      Using synchrotron small-angle X-ray scattering (SAXS) we
                      determine the buffer specificity of the pH-dependent
                      structure of ionizable lipid/cholesterol/water mesophases
                      that serve as model systems for the LNP core phase. The
                      results show that the phase transition from inverse micellar
                      to inverse hexagonal with decreasing pH is shifted to a
                      lower transition pH for acetate and phosphate compared with
                      citrate buffer. Based on continuum theory and ion-specific
                      adsorption obtained from all-atom MD simulations, we propose
                      a mechanism for buffer specificity. Citrate stabilizes the
                      inverse hexagonal phase thus shifting the formation of HII
                      to a higher pH. By contrast, phosphate and acetate stabilize
                      LII. It stands to reason that the inverse micellar to
                      inverse hexagonal transition, which is facilitated in
                      citrate buffer, enables a sensitized pH response of the LNP
                      core phase. This, in turn, enhances endosomal release
                      efficiency and accounts for the earlier onset of gene
                      expression observed in LNPs prepared with citrate buffer.},
      cin          = {EMBL-User / EMBL},
      ddc          = {540},
      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 / EXP:(DE-H253)P-P62-20221101},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40074542},
      UT           = {WOS:001444258800001},
      doi          = {10.1021/acsnano.4c14098},
      url          = {https://bib-pubdb1.desy.de/record/626433},
}