Cell medium-dependent dynamic modulation of size and structural transformations of binary phospholipid/ω-3 fatty acid liquid crystalline nano-self-assemblies: Implications in interpretation of cell uptake studies
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Cell medium-dependent dynamic modulation of size and structural transformations of binary phospholipid/ω-3 fatty acid liquid crystalline nano-self-assemblies : Implications in interpretation of cell uptake studies. / Bor, Gizem; Salentinig, Stefan; Şahin, Evrim; Nur Ödevci, Begüm; Roursgaard, Martin; Liccardo, Letizia; Hamerlik, Petra; Moghimi, Seyed Moein; Yaghmur, Anan.
I: Journal of Colloid and Interface Science, Bind 606, 2022, s. 464-479.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Cell medium-dependent dynamic modulation of size and structural transformations of binary phospholipid/ω-3 fatty acid liquid crystalline nano-self-assemblies
T2 - Implications in interpretation of cell uptake studies
AU - Bor, Gizem
AU - Salentinig, Stefan
AU - Şahin, Evrim
AU - Nur Ödevci, Begüm
AU - Roursgaard, Martin
AU - Liccardo, Letizia
AU - Hamerlik, Petra
AU - Moghimi, Seyed Moein
AU - Yaghmur, Anan
N1 - Funding Information: Financial support by the Danish Council for Independent Research | Technology and Production Sciences, reference DFF-7017-00065 (to AY & SMM) is gratefully acknowledged. AY further acknowledges financial support from the Danish Natural Sciences Research Council (DanScatt) for SAXS experiments. The authors are grateful to the beamline scientist Dr. Heinz Amenitsch (Institute of Inorganic Chemistry, Graz University of Technology) for the technical support at the Austrian SAXS beamline (ELETTRA, Trieste, Italy). They thank also Tillman Pape (Core Facility for Integrated Microscopy, University of Copenhagen) for the technical assistance with cryo-TEM imaging, and Dr. Tom André Jos Vosh and Cecilia Cerretani (Department of Chemistry, University of Copenhagen) for their support and technical assistance with quantum yield measurements. The authors acknowledge the CERIC-ERIC Consortium for the access to experimental facilities and financial support. Funding Information: Financial support by the Danish Council for Independent Research | Technology and Production Sciences, reference DFF-7017-00065 (to AY & SMM) is gratefully acknowledged. AY further acknowledges financial support from the Danish Natural Sciences Research Council (DanScatt) for SAXS experiments. The authors are grateful to the beamline scientist Dr. Heinz Amenitsch (Institute of Inorganic Chemistry, Graz University of Technology) for the technical support at the Austrian SAXS beamline (ELETTRA, Trieste, Italy). They thank also Tillman Pape (Core Facility for Integrated Microscopy, University of Copenhagen) for the technical assistance with cryo-TEM imaging, and Dr. Tom Andr? Jos Vosh and Cecilia Cerretani (Department of Chemistry, University of Copenhagen) for their support and technical assistance with quantum yield measurements. The authors acknowledge the CERIC-ERIC Consortium for the access to experimental facilities and financial support. Publisher Copyright: © 2021 The Author(s)
PY - 2022
Y1 - 2022
N2 - Lyotropic non-lamellar liquid crystalline (LLC) nanoparticles, with their tunable structural features and capability of loading a wide range of drugs and reporter probes, are emerging as versatile injectable nanopharmaceuticals. Secondary emulsifiers, such as Pluronic block copolymers, are commonly used for colloidal stabilization of LLC nanoparticles, but their inclusion often compromises the biological safety (e.g., poor hemocompatibility and enhanced cytotoxicity) of the formulation. Here, we introduce a library of colloidally stable, structurally tunable, and pH-responsive lamellar and non-lamellar liquid crystalline nanoparticles from binary mixtures of a phospholipid (phosphatidylglycerol) and three types of omega-3 fatty acids (ω-3 PUFAs), prepared in the absence of a secondary emulsifier and organic solvents. We study formulation size distribution, morphological heterogeneity, and the arrangement of their internal self-assembled architectures by nanoparticle tracking analysis, synchrotron small-angle X-ray scattering, and cryo-transmission electron microscopy. The results show the influence of type and concentration of ω-3 PUFAs in nanoparticle structural transitions spanning from a lamellar (Lα) phase to inverse discontinuous (micellar) cubic Fd3m and hexagonal phase (H2) phases, respectively. We further report on cell-culture medium-dependent dynamic fluctuations in nanoparticle size, number and morphology, and simultaneously monitor uptake kinetics in two human cell lines. We discuss the role of these multiparametric biophysical transformations on nanoparticle-cell interaction kinetics and internalization mechanisms. Collectively, our findings contribute to the understanding of fundamental steps that are imperative for improved engineering of LLC nanoparticles with necessary attributes for pharmaceutical development.
AB - Lyotropic non-lamellar liquid crystalline (LLC) nanoparticles, with their tunable structural features and capability of loading a wide range of drugs and reporter probes, are emerging as versatile injectable nanopharmaceuticals. Secondary emulsifiers, such as Pluronic block copolymers, are commonly used for colloidal stabilization of LLC nanoparticles, but their inclusion often compromises the biological safety (e.g., poor hemocompatibility and enhanced cytotoxicity) of the formulation. Here, we introduce a library of colloidally stable, structurally tunable, and pH-responsive lamellar and non-lamellar liquid crystalline nanoparticles from binary mixtures of a phospholipid (phosphatidylglycerol) and three types of omega-3 fatty acids (ω-3 PUFAs), prepared in the absence of a secondary emulsifier and organic solvents. We study formulation size distribution, morphological heterogeneity, and the arrangement of their internal self-assembled architectures by nanoparticle tracking analysis, synchrotron small-angle X-ray scattering, and cryo-transmission electron microscopy. The results show the influence of type and concentration of ω-3 PUFAs in nanoparticle structural transitions spanning from a lamellar (Lα) phase to inverse discontinuous (micellar) cubic Fd3m and hexagonal phase (H2) phases, respectively. We further report on cell-culture medium-dependent dynamic fluctuations in nanoparticle size, number and morphology, and simultaneously monitor uptake kinetics in two human cell lines. We discuss the role of these multiparametric biophysical transformations on nanoparticle-cell interaction kinetics and internalization mechanisms. Collectively, our findings contribute to the understanding of fundamental steps that are imperative for improved engineering of LLC nanoparticles with necessary attributes for pharmaceutical development.
KW - Cryogenic transmission electron microscopy
KW - Glioblastoma multiforme T10 cells
KW - Hexosomes
KW - ISAsomes
KW - Micellar cubosomes
KW - Monocytic THP-1 cells
KW - Synchrotron small angle X-ray scattering
U2 - 10.1016/j.jcis.2021.07.149
DO - 10.1016/j.jcis.2021.07.149
M3 - Journal article
C2 - 34399363
AN - SCOPUS:85112345721
VL - 606
SP - 464
EP - 479
JO - Journal of Colloid and Interface Science
JF - Journal of Colloid and Interface Science
SN - 0021-9797
ER -
ID: 276656669