Head on Comparison of Self- and Nano-Assemblies of Gamma Peptide Nucleic Acid Amphiphiles

Malik, Shipra; Kumar, Vikas; Liu, Chung‐Hao; Shih, Kuo‐Chih; Krueger, Susan; Nieh, Mu‐Ping; Bahal, Raman

doi:10.1002/adfm.202109552

Title: Head on Comparison of Self- and Nano-Assemblies of Gamma Peptide Nucleic Acid Amphiphiles

Journal Article · Fri Nov 05 00:00:00 EDT 2021 · Advanced Functional Materials

DOI:https://doi.org/10.1002/adfm.202109552· OSTI ID:1981341

Malik, Shipra ^[1]; Kumar, Vikas ^[1]; Liu, Chung‐Hao ^[1]; Shih, Kuo‐Chih ^[1]; Krueger, Susan ^[2]; Nieh, Mu‐Ping ^[1];

^[1]

Univ. of Connecticut, Storrs, CT (United States)
National Inst. of Standards and Technology (NIST), Gaithersburg, MD (United States)

Peptide nucleic acids (PNAs) are nucleic acid analogs with hybridization properties and enzymatic stability superior to that of DNA. In addition to gene targeting applications, PNAs have garnered significant attention as bio-polymers due to the Watson–Crick-based molecular recognition and flexibility of synthesis. Here, in this work, PNA amphiphiles are engineered using chemically modified gamma PNA (8 mer in length) containing hydrophilic diethylene glycol units at the gamma position and covalently conjugated lauric acid (C12) as a hydrophobic moiety. Gamma PNA ($$\gamma$$PNA) amphiphiles self-assemble into spherical vesicles. Further, nano-assemblies (NA) are formulated using the amphiphilic $$\gamma$$PNA as a polymer via ethanol injection-based protocols. Comprehensive head-on comparison of the physicochemical and cellular uptake properties of PNA derived self- and NA is performed. Small-angle neutron and X-ray scattering analysis reveal ellipsoidal morphology of $$\gamma$$PNA NA that results in superior cellular delivery compate to the spherical self-assembly. Next, the functional activities of $$\gamma$$PNA self-and NA in lymphoma cells via multiple endpoints, including gene expression, cell viability, and apoptosis-based assays are compared. Overall, it is established that $$\gamma$$PNA amphiphile is a functionally active bio-polymer to formulate NA for a wide range of biomedical applications.

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Research Organization:: Brookhaven National Laboratory (BNL), Upton, NY (United States). National Synchrotron Light Source II (NSLS-II)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities (SUF); USDOE Office of Science (SC), Biological and Environmental Research (BER); National Science Foundation (NSF); National Institutes of Health (NIH)

Grant/Contract Number:: SC0012704; KP1607011; DMR-2010792; DMR-0520547; CA241194-01A1; HL147028-01A1; P30GM133893

OSTI ID:: 1981341

Alternate ID(s):: OSTI ID: 1829181

Journal Information:: Advanced Functional Materials, Vol. 32, Issue 7; ISSN 1616-301X

Publisher:: WileyCopyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
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peptide nucleic acid amphiphiles
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Title: Head on Comparison of Self- and Nano-Assemblies of Gamma Peptide Nucleic Acid Amphiphiles

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