Abstract
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, 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 (γ PNA) amphiphiles self-assemble into spherical vesicles. Further, nano-assemblies (NA) are formulated using the amphiphilic γ 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 γ PNA NA that results in superior cellular delivery compate to the spherical self-assembly. Next, the functional activities of γ 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 γ PNA amphiphile is a functionally active bio-polymer to formulate NA for a wide range of biomedical applications.
| Original language | English |
|---|---|
| Article number | 2109552 |
| Journal | Advanced Functional Materials |
| Volume | 32 |
| Issue number | 7 |
| DOIs | |
| State | Published - Feb 9 2022 |
| Externally published | Yes |
Funding
Access to SANS was provided by the Center for High Resolution Neutron Scattering, a partnership between the National Institute of Standards and Technology and the National Science Foundation under Agreement no: DMR-2010792. Certain commercial equipment, instruments, materials, suppliers, or software are identified in this paper to foster understanding. Such identification does not imply recommendation or endorsement by the National Institute of Standards and Technology, nor does it imply that the materials or equipment identified are necessarily the best available for the purpose. The authors would like to thank Dr. Lin Yang for his help with collecting the SAXS data at 16-ID LiX beamline of the National Synchrotron Light Source II, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Brookhaven National Laboratory under Contract no. DE-SC0012704. This work was supported by Hood Foundation award and NIH (R01) (CA241194-01A1 and HL147028-01A1) grant provided to R.B. The Center for BioMolecular Structure (CBMS) is primarily supported by the National Institutes of Health, National Institute of General Medical Sciences (NIGMS) through a Center Core P30 Grant (P30GM133893), and by the DOE Office of Biological and Environmental Research (KP1607011). The small-angle neutron and X-ray scattering analysis benefited from the use of the SasView application, originally developed under NSF Award DMR-0520547. SasView also contains code developed with funding from the EU Horizon 2020 programme under the SINE2020 project Grant No 654000. Access to SANS was provided by the Center for High Resolution Neutron Scattering, a partnership between the National Institute of Standards and Technology and the National Science Foundation under Agreement no: DMR‐2010792. Certain commercial equipment, instruments, materials, suppliers, or software are identified in this paper to foster understanding. Such identification does not imply recommendation or endorsement by the National Institute of Standards and Technology, nor does it imply that the materials or equipment identified are necessarily the best available for the purpose. The authors would like to thank Dr. Lin Yang for his help with collecting the SAXS data at 16‐ID LiX beamline of the National Synchrotron Light Source II, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Brookhaven National Laboratory under Contract no. DE‐SC0012704. This work was supported by Hood Foundation award and NIH (R01) (CA241194‐01A1 and HL147028‐01A1) grant provided to R.B. The Center for BioMolecular Structure (CBMS) is primarily supported by the National Institutes of Health, National Institute of General Medical Sciences (NIGMS) through a Center Core P30 Grant (P30GM133893), and by the DOE Office of Biological and Environmental Research (KP1607011). The small‐angle neutron and X‐ray scattering analysis benefited from the use of the SasView application, originally developed under NSF Award DMR‐0520547. SasView also contains code developed with funding from the EU Horizon 2020 programme under the SINE2020 project Grant No 654000.
| Funders | Funder number |
|---|---|
| National Science Foundation | DMR‐2010792, DMR-0520547 |
| National Institutes of Health | R01, CA241194‐01A1, HL147028‐01A1 |
| U.S. Department of Energy | |
| National Institute of General Medical Sciences | P30GM133893 |
| National Institute of Standards and Technology | |
| Charles H. Hood Foundation | |
| Office of Science | |
| Biological and Environmental Research | KP1607011 |
| Brookhaven National Laboratory | DE‐SC0012704 |
| Horizon 2020 Framework Programme | 654000 |
Keywords
- gamma peptide nucleic acids
- micro-RNA-155
- nano-assemblies
- peptide nucleic acid amphiphiles
- self-assembly
