Campus Units

Chemical and Biological Engineering, Chemistry

Document Type

Article

Research Focus Area

Health Care Technology and Biomedical Engineering

Publication Version

Published Version

Publication Date

3-18-2014

Journal or Book Title

RSC Advances

Volume

4

Issue

30

First Page

15655

Last Page

15663

DOI

10.1039/C3RA47687A

Abstract

We report the synthesis of a family of amphiphilic pentablock polymers with different cationic blocks and with controlled architectures as potential vaccine carriers for subunit vaccines. The temperature and pH-dependent micellization and gelation of these pentablock copolymers can provide a depot for sustained protein and gene delivery. The amphiphilic central triblock promotes cellular endocytosis, good gene delivery and has been used effectively as a vaccine adjuvant. The pentablock copolymer outer blocks condense DNA spontaneously as a result of electrostatic interactions for sustained combinational therapy. This family of polymers with different cationic groups was evaluated based on DNA complexation-ability and cytotoxicity to select promising candidates as DNA-based subunit vaccine adjuvants. Modification of other polymer systems with carbohydrates like mannose has been shown to enhance immunogenicity by activating pattern recognition receptors on antigen presenting cells and increasing uptake in these cells. Here, we report the synthesis of a virus-mimicking pentablock copolymer vaccine platform by successful functionalization of these polymers with mannose through an azide–alkyne Huisgen cycloaddition. The synthesis of a mannoside with the alkyne linker was achieved by a recently reported bismuth(V)-mediated activation of a thioglycoside that proved to leave the alkyne intact. The carbohydrate modification was shown not to interfere with the ability of these virus-mimicking block copolymers to complex DNA, thereby making this family of modified materials promising candidates for DNA-based vaccine delivery.

Comments

This article is published as Adams, J. R., M. Goswami, N. L. B. Pohl, and S. K. Mallapragada. "Synthesis and functionalization of virus-mimicking cationic block copolymers with pathogen-associated carbohydrates as potential vaccine adjuvants." RSC Advances 4, no. 30 (2014): 15655-15663. DOI: 10.1039/C3RA47687A. Posted with permission.

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Copyright Owner

The Royal Society of Chemistry

Language

en

File Format

application/pdf

Share

COinS