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Title: Lights on: Dye dequenching reveals polymersome fusion with polymer, lipid and stealth lipid vesicles

Abstract

In this study, we develop a quantitative dye dequenching technique for the measurement of polymersome fusion, using it to characterize the salt mediated, mechanically-induced fusion of polymersomes with polymer, lipid, and so-called stealth lipid vesicles. While dye dequenching has been used to quantitatively explore liposome fusion in the past, this is the first use of dye dequenching to measure polymersome fusion of which we are aware. In addition to providing quantitative results, dye dequenching is ideal for detecting fusion in instances where DLS results would be ambiguous, such as low yield levels and size ranges outside the capabilities of DLS. The dye chosen for this study was a cyanine derivative, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide (DiR), which proved to provide excellent data on the extent of polymersome fusion. Using this technique, we have shown the limited fusion capabilities of polymersome/liposome heterofusion, notably DOPC vesicles fusing with polymersomes at half the efficiency of polymersome homofusion and DPPC vesicles showing virtually no fusion. In addition to these key heterofusion experiments, we determined the broad applicability of dye dequenching in measuring kinetic rates of polymersome fusion; and showed that even at elevated temperatures or over multiple weeks' time, no polymersome fusion occurred without agitation. Stealth liposomesmore » formed from DPPC and PEO-functionalized lipid, however, fused with polymersomes and stealth liposomes with relatively high efficiency, lending support to our hypothesis that the response of the PEO corona to salt is a key factor in the fusion process. This last finding suggests that although the conjugation of PEO to lipids increases vesicle biocompatibility and enables their longer circulation times, it also renders the vesicles subject to destabilization under high salt and shear (e.g. in the circulatory system) that may lead to, in this case, fusion.« less

Authors:
 [1];  [2];  [3];  [2];  [3];  [1]
  1. Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)
  2. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
  3. New Mexico State Univ., Las Cruces, NM (United States)
Publication Date:
Research Org.:
Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES); USDOE National Nuclear Security Administration (NNSA)
OSTI Identifier:
1239980
Alternate Identifier(s):
OSTI ID: 1396438
Report Number(s):
SAND-2015-11121J
Journal ID: ISSN 0032-3861; PII: S0032386115304274
Grant/Contract Number:  
AC04-94AL85000
Resource Type:
Accepted Manuscript
Journal Name:
Polymer
Additional Journal Information:
Journal Volume: 83; Journal Issue: C; Journal ID: ISSN 0032-3861
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; polymersome; fusion; liposome; polymer; lipid; quenching; dye

Citation Formats

Henderson, Ian M., Collins, Aaron M., Quintana, Hope A., Montaño, Gabriel A., Martinez, Julio A., and Paxton, Walter F. Lights on: Dye dequenching reveals polymersome fusion with polymer, lipid and stealth lipid vesicles. United States: N. p., 2015. Web. https://doi.org/10.1016/j.polymer.2015.12.014.
Henderson, Ian M., Collins, Aaron M., Quintana, Hope A., Montaño, Gabriel A., Martinez, Julio A., & Paxton, Walter F. Lights on: Dye dequenching reveals polymersome fusion with polymer, lipid and stealth lipid vesicles. United States. https://doi.org/10.1016/j.polymer.2015.12.014
Henderson, Ian M., Collins, Aaron M., Quintana, Hope A., Montaño, Gabriel A., Martinez, Julio A., and Paxton, Walter F. Sun . "Lights on: Dye dequenching reveals polymersome fusion with polymer, lipid and stealth lipid vesicles". United States. https://doi.org/10.1016/j.polymer.2015.12.014. https://www.osti.gov/servlets/purl/1239980.
@article{osti_1239980,
title = {Lights on: Dye dequenching reveals polymersome fusion with polymer, lipid and stealth lipid vesicles},
author = {Henderson, Ian M. and Collins, Aaron M. and Quintana, Hope A. and Montaño, Gabriel A. and Martinez, Julio A. and Paxton, Walter F.},
abstractNote = {In this study, we develop a quantitative dye dequenching technique for the measurement of polymersome fusion, using it to characterize the salt mediated, mechanically-induced fusion of polymersomes with polymer, lipid, and so-called stealth lipid vesicles. While dye dequenching has been used to quantitatively explore liposome fusion in the past, this is the first use of dye dequenching to measure polymersome fusion of which we are aware. In addition to providing quantitative results, dye dequenching is ideal for detecting fusion in instances where DLS results would be ambiguous, such as low yield levels and size ranges outside the capabilities of DLS. The dye chosen for this study was a cyanine derivative, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide (DiR), which proved to provide excellent data on the extent of polymersome fusion. Using this technique, we have shown the limited fusion capabilities of polymersome/liposome heterofusion, notably DOPC vesicles fusing with polymersomes at half the efficiency of polymersome homofusion and DPPC vesicles showing virtually no fusion. In addition to these key heterofusion experiments, we determined the broad applicability of dye dequenching in measuring kinetic rates of polymersome fusion; and showed that even at elevated temperatures or over multiple weeks' time, no polymersome fusion occurred without agitation. Stealth liposomes formed from DPPC and PEO-functionalized lipid, however, fused with polymersomes and stealth liposomes with relatively high efficiency, lending support to our hypothesis that the response of the PEO corona to salt is a key factor in the fusion process. This last finding suggests that although the conjugation of PEO to lipids increases vesicle biocompatibility and enables their longer circulation times, it also renders the vesicles subject to destabilization under high salt and shear (e.g. in the circulatory system) that may lead to, in this case, fusion.},
doi = {10.1016/j.polymer.2015.12.014},
journal = {Polymer},
number = C,
volume = 83,
place = {United States},
year = {2015},
month = {12}
}

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