skip to main content
DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Amphiphilic Polypeptoids Rupture Vesicle Bilayers To Form Peptoid–Lipid Fragments Effective in Enhancing Hydrophobic Drug Delivery

Abstract

Peptoids are highly biocompatible pseudopeptidic polyglycines with designable substituents on the nitrogen atoms. The therapeutic and drug-carrying potential of these materials requires a fundamental understanding of their interactions with lipid bilayers. Here, we use amphiphilic polypeptoids with up to 100 monomeric units where a significant fraction (26%) of the nitrogen atoms are functionalized with decyl groups (hydrophobes) that insert into the lipid bilayer through the hydrophobic effect. These hydrophobically modified polypeptoids (HMPs) insert their hydrophobes into lipid bilayers creating instabilities that lead to the rupture of vesicles. At low HMP concentrations, such rupture leads to the creation of large fragments which remarkably anchor to intact vesicles through the hydrophobic effect. At high HMP concentrations, all vesicles rupture to smaller HMP–lipid fragments of the order of 10 nm. We show that the technique for such nanoscale polymer–lipid fragments can be exploited to sustain highly hydrophobic drug species in solution. Using the kinase inhibitor, Sorafenib as a model drug, it is shown that HMP–lipid fragments containing the drug can efficiently enter a hepatocellular carcinoma cell line (Huh 7.5), indicating the use of such fragments as drug delivery nanocarriers.

Authors:
 [1];  [1];  [1];  [2];  [2];  [1];  [1];  [1]; ORCiD logo [2]; ORCiD logo [1]
  1. Tulane University, New Orleans, LA (United States)
  2. Louisiana State University, Baton Rouge, LA (United States)
Publication Date:
Research Org.:
Louisiana State Univ., Baton Rouge, LA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES); National Science Foundation (NSF)
OSTI Identifier:
1672152
Alternate Identifier(s):
OSTI ID: 1615947
Grant/Contract Number:  
SC0012432; 1805608
Resource Type:
Accepted Manuscript
Journal Name:
Langmuir
Additional Journal Information:
Journal Volume: 35; Journal Issue: 47; Journal ID: ISSN 0743-7463
Publisher:
American Chemical Society
Country of Publication:
United States
Language:
English
Subject:
75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND SUPERFLUIDITY; Vesicles; Thin films; Lipids; Hydrophobicity; Hydration

Citation Formats

Zhang, Yueheng, Heidari, Zahra, Su, Yang, Yu, Tianyi, Xuan, Sunting, Omarova, Marzhana, Aydin, Yucel, Dash, Srikanta, Zhang, Donghui, and John, Vijay. Amphiphilic Polypeptoids Rupture Vesicle Bilayers To Form Peptoid–Lipid Fragments Effective in Enhancing Hydrophobic Drug Delivery. United States: N. p., 2019. Web. https://doi.org/10.1021/acs.langmuir.9b03322.
Zhang, Yueheng, Heidari, Zahra, Su, Yang, Yu, Tianyi, Xuan, Sunting, Omarova, Marzhana, Aydin, Yucel, Dash, Srikanta, Zhang, Donghui, & John, Vijay. Amphiphilic Polypeptoids Rupture Vesicle Bilayers To Form Peptoid–Lipid Fragments Effective in Enhancing Hydrophobic Drug Delivery. United States. https://doi.org/10.1021/acs.langmuir.9b03322
Zhang, Yueheng, Heidari, Zahra, Su, Yang, Yu, Tianyi, Xuan, Sunting, Omarova, Marzhana, Aydin, Yucel, Dash, Srikanta, Zhang, Donghui, and John, Vijay. Tue . "Amphiphilic Polypeptoids Rupture Vesicle Bilayers To Form Peptoid–Lipid Fragments Effective in Enhancing Hydrophobic Drug Delivery". United States. https://doi.org/10.1021/acs.langmuir.9b03322. https://www.osti.gov/servlets/purl/1672152.
@article{osti_1672152,
title = {Amphiphilic Polypeptoids Rupture Vesicle Bilayers To Form Peptoid–Lipid Fragments Effective in Enhancing Hydrophobic Drug Delivery},
author = {Zhang, Yueheng and Heidari, Zahra and Su, Yang and Yu, Tianyi and Xuan, Sunting and Omarova, Marzhana and Aydin, Yucel and Dash, Srikanta and Zhang, Donghui and John, Vijay},
abstractNote = {Peptoids are highly biocompatible pseudopeptidic polyglycines with designable substituents on the nitrogen atoms. The therapeutic and drug-carrying potential of these materials requires a fundamental understanding of their interactions with lipid bilayers. Here, we use amphiphilic polypeptoids with up to 100 monomeric units where a significant fraction (26%) of the nitrogen atoms are functionalized with decyl groups (hydrophobes) that insert into the lipid bilayer through the hydrophobic effect. These hydrophobically modified polypeptoids (HMPs) insert their hydrophobes into lipid bilayers creating instabilities that lead to the rupture of vesicles. At low HMP concentrations, such rupture leads to the creation of large fragments which remarkably anchor to intact vesicles through the hydrophobic effect. At high HMP concentrations, all vesicles rupture to smaller HMP–lipid fragments of the order of 10 nm. We show that the technique for such nanoscale polymer–lipid fragments can be exploited to sustain highly hydrophobic drug species in solution. Using the kinase inhibitor, Sorafenib as a model drug, it is shown that HMP–lipid fragments containing the drug can efficiently enter a hepatocellular carcinoma cell line (Huh 7.5), indicating the use of such fragments as drug delivery nanocarriers.},
doi = {10.1021/acs.langmuir.9b03322},
journal = {Langmuir},
number = 47,
volume = 35,
place = {United States},
year = {2019},
month = {11}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Save / Share: