A universal discoidal nanoplatform for the intracellular delivery of PNAs. Issue 26 (12th June 2019)

• Record Type: Journal Article
• Authors: Tahmasbi Rad, Armin; Malik, Shipra; Yang, Lin; Oberoi-Khanuja, Tripat Kaur; Nieh, Mu-Ping; Bahal, Raman
• Is Part Of: Nanoscale. Volume 11:Issue 26(2019)
• Page Start: 12517
• Page End: 12529
• Publication Date: 2019-06-12
• Subjects: Nanoscience -- Periodicals; Nanotechnology -- Periodicals; 620.505
• DOI: 10.1039/c9nr03667a
• Languages: English
• ISSNs: 2040-3364

Abstract

Abstract : Peptide nucleic acids (PNAs) have gained considerable attention due to their remarkable potential in gene editing and targeting-based strategies. Abstract : 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 dye-conjugated 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.