Ellipsoidal polyaspartamide polymersomes with enhanced cell-targeting ability

Nano-sized polymersomes functionalized with peptides are being increasingly studied for targeted delivery of diagnostic and therapeutic molecules. Earlier computational studies have suggested that ellipsoidal nanoparticles, compared to spherical ones, display enhanced binding efficiency with target cells, but this has not yet been experimentally validated. We hypothesized that hydrophilic polymer chains coupled to vesicle-forming polymers would result in ellipsoidal polymersomes. In addition, ellipsoidal polymersomes modified with cell adhesion peptides bind with target cells more actively than spherical ones. We examined this hypothesis by substituting polyaspartamide with octadecyl chains and varying numbers of poly(ethylene glycol) (PEG) chains. Increasing the degree of substitution of PEG from 0.5 to 1.0 wt% drove the polymer to self-assemble into an ellipsoidal polymersome with an aspect ratio of 2.1. Further modification of these ellipsoidal polymersomes with peptides containing an Arg-Gly-Asp sequence (RGD peptides) led to a significant increase in the rate of association and decrease in the rate of dissociation with a substrate coated with alphav-beta3 integrins. In addition, in a circulation-mimicking flow, the ellipsoidal polymersomes linked with RGD peptides adhered to target tissues more favorably than their spherical equivalents did. Overall, the results of this study will greatly serve to improve the efficiency of targeted delivery of a wide array of polymersomes loaded with various biomedical modalities.

Name thesis:degree_name

M.S.

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Chemical Engineering

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2012

Author dc:creator

• Lai, Mei-Hsiu

Contributors dc:contributor

• Kong, Hyun Joon

• polymersomes

Statement dc:rights

• Copyright 2011 Mei-Hsiu Lai

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/29549

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/29549