Structure–Property Relationships of Oligonucleotide Polyelectrolyte Complex Micelles

Lueckheide, Michael; Vieregg, Jeffrey R.; Bologna, Alex J.; Leon, Lorraine; Tirrell, Matthew V.

doi:10.1021/acs.nanolett.8b03132

Title: Structure–Property Relationships of Oligonucleotide Polyelectrolyte Complex Micelles

Journal Article · Fri Oct 19 00:00:00 EDT 2018 · Nano Letters

DOI:https://doi.org/10.1021/acs.nanolett.8b03132· OSTI ID:1514885

^[1];

^[1]; Bologna, Alex J. ^[1]; Leon, Lorraine ^[2]; Tirrell, Matthew V. ^[3]

Univ. of Chicago, IL (United States)
Univ. of Central Florida, Orlando, FL (United States)
Univ. of Chicago, IL (United States); Argonne National Lab. (ANL), Lemont, IL (United States)

Polyelectrolyte complex micelles (PCMs), nanoparticles formed by electrostatic self-assembly of charged polymers with charged-neutral hydrophilic block copolymers, offer a potential solution to the challenging problem of delivering therapeutic nucleic acids into cells and organisms. Promising results have been reported in vitro and in animal models but basic structure property relationships are largely lacking, and some reports have suggested that double stranded nucleic acids cannot form PCMs due to their high bending rigidity. Here, we report on a study of PCMs formed by DNA oligonucleotides of varied length and hybridization state and poly(L)lysine-poly(ethylene glycol) block copolymers with varying block lengths. We employ a multimodal characterization strategy combining small-angle X-ray scattering (SAXS), multiangle light scattering (MALS), and cryo-electron microscopy (cryo-TEM) to simultaneously probe the morphology and internal structure of the micelles. Over a wide range of parameters, we find that nanoparticle shape is controlled primarily by the hybridization state of the oligonucleotides with single-stranded oligonucleotides forming spheroidal micelles and double stranded oligonucleotides forming wormlike micelles. The length of the charged block controls the radius of the nanoparticle, while oligonucleotide length appears to have little impact on either size or shape. At smaller length scales, we observe parallel packing of DNA helices inside the double-stranded nanoparticles, consistent with results from condensed genomic DNA. We additionally describe salt- and thermal-annealing protocols for preparing PCMs with high repeatability and low polydispersity. Together, these results provide a capability to rationally design PCMs with desired sizes and shapes that should greatly assist development of this promising delivery technology.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22). Materials Sciences & Engineering Division; USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities Division

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1514885

Journal Information:: Nano Letters, Vol. 18, Issue 11; ISSN 1530-6984

Publisher:: American Chemical SocietyCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 47 works

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Engineering Peptide-Based Polyelectrolyte Complexes with Increased Hydrophobicity Tabandeh, Sara; Leon, Lorraine Molecules, Vol. 24, Issue 5 https://doi.org/10.3390/molecules24050868	journal	March 2019
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Related Subjects

77 NANOSCIENCE AND NANOTECHNOLOGY
Coacervation
Nanoparticles
Oligonucleotides
Phase separation
complexation
polyelectrolytes