Engineering cell membrane by liposomal treatment modulates endocytosis of nanomaterials in tumor cells

Abstract: Nanomedicines, including liposomes and polymeric nanoparticles, can target tumor cells via receptor-mediated endocytosis. However, the role of biophysics of cell lipid bilayer in nanoparticle uptake pathway remains unexplored. Nanomedicines are taken up mainly via clathrin/caveolae-mediated endocytosis, which depends on membrane deformation. Since phase behavior influences deformability of lipid bilayers, we postulated that phase behavior of cell membranes could impact endocytosis of nanomedicines.
In second section of the dissertation, we inquired whether endocytosis of liposomes, a lipid bilayer-derived vesicle, depends on their phase behavior. First, it was shown that the endocytosis of liposomes was related to their phase behavior and increasing membrane fluidity diminished dynamin-dependent endocytosis of liposomes. Since liposomal treatment can modify the phase behavior of cell membranes, we further theorized that altering phase behavior of cell membranes by liposomal pre-treatment could impact endocytosis of nanoparticles. Using rhodamine-labeled PLGA nanoparticles and NBD-cholesterol labeled liposomes (100 nm) as models for nanomedicine, and employing giant plasma membrane vesicles (GPMV) derived from MDA-MB-231 as model for the cell membrane the effect of liposomal treatment on nanomedicine uptake as investigated. Characterization of the stiffness of GPMV using flicker spectroscopy revealed that liposomal treatment can modify the stiffness and lipid composition of cell membrane, thereby modulating endocytic uptake of PLGA NPs. The increased cell membrane stiffness was found to elevate cellular uptake of NPs by promoting clathrin/caveolae/dynamin-mediated endocytosis.
Cellular uptake of lipid vesicles is important for cell communication and drug delivery. Since lipid vesicles can be taken up by the cells upon interacting with plasma membranes, in section three of the dissertation, it was postulated that the pattern of membrane interaction would determine endocytic uptake mechanism of liposomes. Since cholesterol can influence the phase behavior and curvature of lipid bilayers, and thereby impacting interaction between lipid bilayers, the role of liposomal free cholesterol in liposome-cell interaction was investigated. We found that efficiency of nonspecific membrane interaction was associated with cellular uptake mechanisms of liposomes and liposomal free cholesterol enhanced the non-specific liposome-cell membrane interaction; resulting diminished caveolae-mediated endocytosis of liposomes.

Since liposomal free cholesterol was shown to promote non-specific interaction between liposome and cell membrane in section four of the dissertation it was hypothesized that the proportion of cholesterol on the cell membrane could impact liposome-cell membrane interaction. By exploiting the high and specific affinity of filipin, a fluorophore, to free cholesterol the proportion of free cholesterol in cell membrane was estimated by staining of GPMV. It was found that pre-treating the cells with liposomes containing different fractions of cholesterol altered the proportion of cholesterol on the cell membrane. Altered proportion of cholesterol on the cell membrane in turn modulated the interaction between cell membrane and fluorescent labeled liposomes. These results in sum suggest that a biophysical strategy to alter the interaction and uptake of nanomedicines by cancer cells through engineering of the cell membrane by liposomal treatment can provide a clear and more precise avenue for enhancing therapeutic efficacy of cancer therapeutics

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch
• Anmerkungen: Universität Freiburg, Dissertation, 2017

Klassifikation und Themen

• Klassifikation: Medizin, Gesundheit
• Schlagwort: Endocytosis ; Cells ; Nanostructured materials ; Liposomes ; Cholesterol ; Tumor

Beteiligte, Orts- und Zeitangaben

• Ereignis: Veröffentlichung
• (wo): Freiburg
• (wer): Universität
• (wann): 2018
• Urheber: Xiang, Shengnan
• Beteiligte Personen und Organisationen: Shastri, V. Prasad ; Albert-Ludwigs-Universität Freiburg. Fakultät für Chemie und Pharmazie

Weitere Informationen

• DOI: 10.6094/UNIFR/14433
• URN: urn:nbn:de:bsz:25-freidok-144333
• Rechteinformation: Kein Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 25.03.2025, 13:56 MEZ