Amino-Acid-Derived Anionic Polyacrylamides with Tailored Hydrophobicity–Physicochemical Properties and Cellular Interactions

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Abstract

Polyanions can internalize into cells via endocytosis without any cell disruption and are therefore interesting materials for biomedical applications. In this study, amino-acid-derived polyanions with different alkyl side-chains are synthesized via postpolymerization modification of poly(pentafluorophenyl acrylate), which is synthesized via reversible addition–fragmentation chain-transfer (RAFT) polymerization, to obtain polyanions with tailored hydrophobicity and alkyl branching. The success of the reaction is verified by size-exclusion chromatography, NMR spectroscopy, and infrared spectroscopy. The hydrophobicity, surface charge, and pH dependence are investigated in detail by titrations, high-performance liquid chromatography, and partition coefficient measurements. Remarkably, the determined p K _a-values for all synthesized polyanions are very similar to those of poly(acrylic acid) (p K _a = 4.5), despite detectable differences in hydrophobicity. Interactions between amino-acid-derived polyanions with L929 fibroblasts reveal very slow cell association as well as accumulation of polymers in the cell membrane. Notably, the more hydrophobic amino-acid-derived polyanions show higher cell association. Our results emphasize the importance of macromolecular engineering toward ideal charge and hydrophobicity for polymer association with cell membranes and internalization. This study further highlights the potential of amino-acid-derived polymers and the diversity they provide for tailoring properties toward drug delivery applications.

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Author and article information

Journal

Journal ID (nlm-ta): ACS Polym Au

Journal ID (iso-abbrev): ACS Polym Au

Journal ID (publisher-id): lg

Journal ID (coden): apaccd

Title: ACS Polymers Au

Publisher: American Chemical Society

ISSN (Electronic): 2694-2453

Publication date (Electronic): 12 March 2024

Publication date Collection: 12 June 2024

Volume: 4

Issue: 3

Pages: 222-234

Affiliations

[† ]Macromolecular Chemistry, University of Bayreuth , Universitätsstraße 30, 95447 Bayreuth, Germany

[‡ ]Laboratory of Organic and Macromolecular Chemistry (IOMC), Friedrich Schiller University Jena , Humboldtstrasse 10, 07743 Jena, Germany

[§ ]Jena Center for Soft Matter (JCSM), Friedrich Schiller University Jena , Philosophenweg 7, 07743 Jena, Germany

[∥ ]Bavarian Polymer Institute , Universitätsstraße 30, 95447 Bayreuth, Germany

Author notes

[* ]mail: meike.leiske@ 123456uni-bayreuth.de .

Author information

Michael Ringleb https://orcid.org/0000-0002-7320-8529

Ulrich S. Schubert https://orcid.org/0000-0003-4978-4670

Anja Traeger https://orcid.org/0000-0001-7734-2293

Meike N. Leiske https://orcid.org/0000-0002-8525-2324

Article

DOI: 10.1021/acspolymersau.3c00048

PMC ID: 11177303

PubMed ID: 38882030

SO-VID: 6ea4f633-82f8-4e14-b0cc-31eced776706

License:

Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works ( https://creativecommons.org/licenses/by-nc-nd/4.0/).

History

Date received : 29 November 2023

Date accepted : 08 February 2024

Date revision received : 07 February 2024

Funding

Funded by: Fonds der Chemischen Industrie, doi 10.13039/100018992;

Award ID: NA

Funded by: ThÃ¼ringer Aufbaubank, doi 10.13039/501100004403;

Award ID: 2021 FGI 0005

Funded by: Bundesministerium fÃ¼r Bildung und Forschung, doi 10.13039/501100002347;

Award ID: 13XP5034A

Funded by: Deutsche Forschungsgemeinschaft, doi 10.13039/501100001659;

Award ID: SFB 1278 - 316213987

Custom metadata

document-id-old-9 lg3c00048

document-id-new-14 lg3c00048

ccc-price

Keywords: polycarboxylate,amino-acid-derived polymer,polyanion,polyelectrolyte,biomimicking polymer,postpolymerization modification,cell association

Data availability:

Keywords: polycarboxylate, amino-acid-derived polymer, polyanion, polyelectrolyte, biomimicking polymer, postpolymerization modification, cell association

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