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

Research output: Contribution to journalJournal articleResearchpeer-review

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.

Original languageEnglish
JournalJournal of Colloid and Interface Science
Volume606
Pages (from-to)464-479
Number of pages16
ISSN0021-9797
DOIs
Publication statusPublished - 2022

Bibliographical note

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)

    Research areas

  • Cryogenic transmission electron microscopy, Glioblastoma multiforme T10 cells, Hexosomes, ISAsomes, Micellar cubosomes, Monocytic THP-1 cells, Synchrotron small angle X-ray scattering

ID: 276656669