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



Shipra Malik, Vikas Kumar, Chung-Hao Liu, Kuo-Chih Shih, Susan T. Krueger, Mu-Ping Neih, Raman Bahal


Peptide nucleic acids (PNAs) are nucleic acid analogs with superior hybridization properties and enzymatic stability than deoxyribonucleic acid (DNA). In addition to gene targeting applications, PNAs have garnered significant attention as bio-polymer due to the Watson-Crick-based molecular recognition and flexibility of synthesis. Here, we engineered PNA amphiphiles 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 (γPNA) amphiphiles self-assemble into spherical vesicles. Further, we formulate nano-assemblies using the amphiphilic γPNA as a polymer via ethanol injection-based protocols. We perform comprehensive head-on comparison of the physicochemical and cellular uptake properties of PNA derived self- and nano-assemblies. Small-angle X-ray scattering (SAXS) and small-angle neutron scattering (SANS) analysis reveal ellipsoidal morphology of γPNA nano-assemblies that results in superior cellular delivery compate to the spherical self-assembly. Next, we compare the functional activities of γPNA self-and nano-assemblies in lymphoma cells via multiple endpoints, including gene expression, cell viability, and apoptosis-based assays. Overall, we establish that γPNA amphiphile is a functionally active bio-polymer to formulate nano-assemblies for a wide range of biomedical applications.
Advanced Functional Materials


gamma peptide nucleic acids, gamma PNAs, nano-assemblies, self-assembly, micro- RNA-155, PNA amphiphiles


Malik, S. , Kumar, V. , Liu, C. , Shih, K. , Krueger, S. , Neih, M. and Bahal, R. (2022), Head on Comparison of Self- and Nano-Assemblies of Gamma Peptide Nucleic Acid Amphiphiles, Advanced Functional Materials, [online], (Accessed May 21, 2024)


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Created February 8, 2022, Updated November 29, 2022