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In Situ Synthesis of Peptide Nucleic Acids in Porous Silicon for Drug Delivery and Biosensing
journal contribution
posted on 2015-12-17, 03:15 authored by Kelsey
R. Beavers, Jeremy W. Mares, Caleb M. Swartz, Yiliang Zhao, Sharon M. Weiss, Craig L. DuvallPeptide nucleic acids (PNA) are a
unique class of synthetic molecules
that have a peptide backbone and can hybridize with nucleic acids.
Here, a versatile method has been developed for the automated, in
situ synthesis of PNA from a porous silicon (PSi) substrate for applications
in gene therapy and biosensing. Nondestructive optical measurements
were performed to monitor single base additions of PNA initiated from
(3-aminopropyl)triethoxysilane attached to the surface of PSi films,
and mass spectrometry was conducted to verify synthesis of the desired
sequence. Comparison of in situ synthesis to postsynthesis surface
conjugation of the full PNA molecules showed that surface mediated,
in situ PNA synthesis increased loading 8-fold. For therapeutic proof-of-concept,
controlled PNA release from PSi films was characterized in phosphate
buffered saline, and PSi nanoparticles fabricated from PSi films containing
in situ grown PNA complementary to micro-RNA (miR) 122 generated significant
anti-miR activity in a Huh7 psiCHECK-miR122 cell line. The applicability
of this platform for biosensing was also demonstrated using optical
measurements that indicated selective hybridization of complementary
DNA target molecules to PNA synthesized in situ on PSi films. These
collective data confirm that we have established a novel PNA–PSi
platform with broad utility in drug delivery and biosensing.