Issue 4, 2023

Net anionic poly(β-amino ester)s: synthesis, pH-dependent behavior, and complexation with cationic cargo

Abstract

As hydrolytically-labile, traditionally-cationic polymers, poly(β-amino ester)s (PBAEs) adeptly complex anionic compounds such as nucleic acids, and release their cargo as the polymer degrades. To engineer fully-degradable polyelectrolyte complexes and delivery vehicles for cationic therapeutics, we sought to invert PBAE net charge to generate net anionic PBAEs. Since PBAEs can carry up to a net charge of +1 per tertiary amine, we synthesized a series of alkyne-functionalized PBAEs that allowed installation of 2 anionic thiol-containing molecules per tertiary amine via a radical thiol–yne reaction. Finding dialysis in aqueous solution to lead to PBAE degradation, we developed a preparative size exclusion chromatography method to remove unreacted thiol from the net anionic PBAEs without triggering hydrolysis. The net anionic PBAEs display non-monotonic solution behavior as a function of pH, being more soluble at pH 4 and 10 than in intermediate pH ranges. Like cationic PBAEs, these net anionic PBAEs degrade in aqueous environments with hydrophobic content-dependent hydrolysis, as determined by 1H NMR spectroscopy. Further, these net anionic PBAEs form complexes with the cationic peptide (glycine-arginine)10, which disintegrate over time as the polymer hydrolyzes. Together, these studies outline a synthesis and purification route to make previously inaccessible net anionic PBAEs with tunable solution and degradation behavior, allowing for user-determined complexation and release rates and providing opportunities for degradable polyelectrolyte complexes and cationic therapeutic delivery.

Graphical abstract: Net anionic poly(β-amino ester)s: synthesis, pH-dependent behavior, and complexation with cationic cargo

Supplementary files

Article information

Article type
Paper
Submitted
14 Oct 2022
Accepted
09 Dec 2022
First published
21 Dec 2022

Polym. Chem., 2023,14, 421-431

Net anionic poly(β-amino ester)s: synthesis, pH-dependent behavior, and complexation with cationic cargo

M. K. Kuenen, A. M. Cuomo, V. P. Gray and R. A. Letteri, Polym. Chem., 2023, 14, 421 DOI: 10.1039/D2PY01319C

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements