Cell mimetic liposomal nanocarriers for tailored delivery of vascular therapeutics

Samuel I. Mattern-Schain, Richard K. Fisher, Philip C. West, Lauren B. Grimsley, Taylor M. Harris, Oscar Grandas, Michael D. Best, Deidra Mountain

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Liposomal delivery systems (LDSs) have been at the forefront of medicinal nanotechnology for over three decades. Increasing LDS association to target cells and cargo delivery is crucial to bolstering overall nanodrug efficacy. Our laboratory aims to develop LDSs for molecular therapeutics aimed at vascular pathology. We have previously established a liposome platform that is an effective delivery system for RNA interference in vascular cell types by using polyethylene glycol (PEG) decorated liposomes bearing an octa-arginine (R8) cell penetrating peptide (CPP). Further tailoring liposome membranes to mimic vascular cell membrane lipid constituents may be a promising strategy for increasing cargo delivery. Here we aimed to develop liposomal formulations that could make use of diacylglycerol (DAG) and phosphatidylserine (PS), naturally occurring lipid species that are known to influence vascular cell function, as a facile and efficient means to increase nanodrug efficacy without compromising clinical viability. We investigated the ability of DAG and PS to amplify the cellular uptake of our previously established LDS platform loaded with small interfering ribonucleic acid (siRNA) cargo. Cellular fluorescence microscopy experiments were performed in conjunction with quantitative cell association assays and cytotoxicity assays to analyze the effect of DAG/PS on the differential delivery of fluorescently-tagged liposomes to vascular smooth muscle cells (VSMCs) and vascular endothelial cells (VECs) and on liposomal-mediated toxicity. In these studies, significant, dose-dependent increases in association to target cells were observed, as well as cell-type specific effects on cell viability. The stability and encapsulation-efficiency of the DAG/PS-modified LDSs were analyzed by standard nanoparticle characterization methods, and siRNA transfection efficacy was quantified to gauge delivery potential as a function of DAG/PS modification. Our results suggest that the signaling lipids tested here imbue our LDS architectures with increased therapeutic potential, without compromising stability, encapsulation efficiency, or biocompatibility, thus presenting a natural strategy to increase nanodrug efficacy and specificity.

Original languageEnglish (US)
Pages (from-to)149-157
Number of pages9
JournalChemistry and Physics of Lipids
Volume218
DOIs
StatePublished - Jan 1 2019

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Phosphatidylserines
Diglycerides
Blood Vessels
Liposomes
Association reactions
RNA
Encapsulation
Assays
Bearings (structural)
Cells
Cell-Penetrating Peptides
Lipids
Therapeutics
Fluorescence microscopy
Endothelial cells
Pathology
Cytotoxicity
Membrane Lipids
Nanotechnology
Biocompatibility

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Cell Biology

Cite this

Cell mimetic liposomal nanocarriers for tailored delivery of vascular therapeutics. / Mattern-Schain, Samuel I.; Fisher, Richard K.; West, Philip C.; Grimsley, Lauren B.; Harris, Taylor M.; Grandas, Oscar; Best, Michael D.; Mountain, Deidra.

In: Chemistry and Physics of Lipids, Vol. 218, 01.01.2019, p. 149-157.

Research output: Contribution to journalArticle

Mattern-Schain, Samuel I. ; Fisher, Richard K. ; West, Philip C. ; Grimsley, Lauren B. ; Harris, Taylor M. ; Grandas, Oscar ; Best, Michael D. ; Mountain, Deidra. / Cell mimetic liposomal nanocarriers for tailored delivery of vascular therapeutics. In: Chemistry and Physics of Lipids. 2019 ; Vol. 218. pp. 149-157.
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