Packaging pDNA by Polymeric ABC Micelles Simultaneously Achieves Colloidal Stability and Structural Control

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11 Scopus citations

Abstract

Compaction of DNA by oppositely charged nanoparticles is a fundamental phenomenon in nature and of great interest to developing therapeutics. In addition, the ability to orthogonally control the composition and structure of interpolyelectrolyte complexes is needed to develop materials for diverse applications. Herein, we systematically investigate the complexation of plasmid DNA and polymeric cationic AB and ABC micelles to explore the influence of micelle outer nonionic corona length on the colloidal stability, size, composition, and structure of the resulting "micelleplexes". The micelles were self-assembled from amphiphilic block polymers, poly(ethylene glycol)-block-poly((2-dimethylamino)ethyl methacrylate)-block-poly(n-butyl methacrylate) (PEG-b-PDMAEMA-b-PnBMA), and PDMAEMA-b-PnBMA with the same Mn of PDMAEMA. These spherical micelles have similar hydrodynamic radii and core sizes, but the Mn of the outer PEG block ranged from 0 to 10 kDa. The colloidal stability of micelleplexes as a function of stoichiometric charge ratio was assessed by turbidimetric titration and was found to dramatically improve with the addition of an outer PEG corona, even as short as 2 kDa. With the use of a combination of dynamic and static light scattering, ζ-potential, and cryogenic transmission electron microscopy, it was found that the size, composition, and structure of micelleplexes are closely correlated with the Mn of the PEG block. Indeed, these micelleplexes were found to adopt beads-on-a-string morphologies that resemble the general structure of chromatin, and the number of micelles per micelleplex systematically decreased with increasing PEG length. These findings demonstrate the power of polycationic micelles to condense DNA into biomimetic structures and provide a mechanistic understanding of nucleic acid complexation and of how micelle architecture affects the properties of micelleplexes, while offering an appealing strategy to control the properties of micelleplexes by tuning a single parameter.

Original languageEnglish (US)
Pages (from-to)11101-11111
Number of pages11
JournalJournal of the American Chemical Society
Volume140
Issue number35
DOIs
StatePublished - Sep 5 2018

How much support was provided by MRSEC?

  • Primary

Reporting period for MRSEC

  • Period 5

PubMed: MeSH publication types

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

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