A universal discoidal nanoplatform for the intracellular delivery of PNAs

Tahmasbi Rad, Armin; Malik, Shipra; Yang, Lin; Oberoi-Khanuja, Tripat Kaur; Nieh, Mu-Ping; Bahal, Raman

doi:10.1039/C9NR03667A

Title: A universal discoidal nanoplatform for the intracellular delivery of PNAs

Journal Article · 28 May 2019 · Nanoscale

DOI: https://doi.org/10.1039/C9NR03667A · OSTI ID:1557110

Tahmasbi Rad, Armin ^[1]; Malik, Shipra ^[1]; Yang, Lin ^[2]; Oberoi-Khanuja, Tripat Kaur ^[3];

^[1];

^[1]

Univ. of Connecticut, Storrs, CT (United States)
Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source II (NSLS-II)
Univ. of California, San Diego, CA (United States)

Peptide nucleic acids (PNAs) have gained considerable attention due to their remarkable potential in gene editing and targeting-based strategies. However, cellular delivery of PNAs remains a challenge in developing their broader therapeutic applications. Here, we investigated a novel complex made of lipid bicelles and PNA-based carriers for the efficient delivery of PNAs. For proof of concept, PNAs targeting microRNA (miR) 210 and 155 were tested. Comprehensive evaluation of positive as well as negative charge-containing bicelles with PNA : lipid ratios of 1 : 100, 1 : 1000, and 1 : 2500 was performed. The negatively charged bicelles with a PNA : lipid molar ratio of 1 : 2500 yielded a discoidal shape with a uniform diameter of ~30 nm and a bilayer thickness of 5 nm, while the positively charged bicellar system contained irregular vesicles after the incorporation of PNA. Small-angle X-ray scattering (SAXS) analysis was performed to provide insight into how the hydrophobic PNAs interact with bicelles. Further, flow cytometry followed by confocal microscopy analyses substantiate the superior transfection efficiency of bicelles containing dyeconjugated antimiR PNAs. Functional analysis also confirmed miR inhibition by PNA oligomers delivered by bicelles. The nanodiscoidal complex opens a new pathway to deliver PNAs, which, on their own, are a great challenge to be endocytosed into cells.

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Research Organization:: Brookhaven National Lab. (BNL), Upton, NY (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)

Grant/Contract Number:: SC0012704

OSTI ID:: 1557110

Report Number(s):: BNL--211968-2019-JAAM

Journal Information:: Nanoscale, Journal Name: Nanoscale Journal Issue: 26 Vol. 11; ISSN NANOHL; ISSN 2040-3364

Publisher:: Royal Society of ChemistryCopyright Statement

Country of Publication:: United States

Language:: English

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