Cation Bulk and pKa Modulate Diblock Polymer Micelle Binding to pDNA

Cristiam F. Santa Chalarca, Rishad J. Dalal, Alejandra Chapa, Mckenna G. Hanson, Theresa M. Reineke

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Polymer-based gene delivery relies on the binding, protection, and final release of nucleic acid cargo using polycations. Engineering polymeric vectors, by exploring novel topologies and cationic moieties, is a promising avenue to improve their performance, which hinges on the development of simple synthetic methods that allow facile preparation. In this work, we focus on cationic micelles formed from block polymers, which are examined as promising gene compaction agents and carriers. In this study, we report the synthesis and assembly of six amphiphilic poly(n-butyl acrylate)-b-poly(cationic acrylamide) diblock polymers with different types of cationic groups ((dialkyl)amine, morpholine, or imidazole) in their hydrophilic corona. The polycations were obtained through the parallel postpolymerization modification of a poly(n-butyl acrylate)-b-poly(pentafluorophenyl acrylate) reactive scaffold, which granted diblock polymers with equivalent degrees of polymerization and subsequent quantitative functionalization with cations of different pKa. Ultrasound-assisted direct dissolution of the polycations in different aqueous buffers (pH = 1-7) afforded micellar structures with low size dispersities and hydrodynamic radii below 100 nm. The formation and properties of micelle-DNA complexes ("micelleplexes") were explored via DLS, zeta potential, and dye-exclusion assays revealing that binding is influenced by the cation type present in the micelle corona where bulkiness and pKa are the drivers of micelleplex formation. Combining parallel synthesis strategies with simple direct dissolution formulation opens opportunities to optimize and expand the range of micelle delivery vehicles available by facile tuning of the composition of the cationic micelle corona.

Original languageEnglish (US)
Pages (from-to)588-594
Number of pages7
JournalACS Macro Letters
Volume11
Issue number4
DOIs
StatePublished - Apr 19 2022

Bibliographical note

Funding Information:
This work was supported primarily by the National Science Foundation (NSF) through the University of Minnesota MRSEC under Award DMR2011401. M.G.H. acknowledges support from the National Science Foundation Graduate Research Fellowship Program (DGE-1839286).

Publisher Copyright:
© 2022 American Chemical Society.

How much support was provided by MRSEC?

  • Primary

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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