In Situ Synthesis of Peptide Nucleic Acids in Porous Silicon for Drug Delivery and Biosensing

Peptide 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...

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Bibliographic Details
Published in:	Bioconjugate chemistry Vol. 25; no. 7; pp. 1192 - 1197
Main Authors:	Beavers, Kelsey R, Mares, Jeremy W, Swartz, Caleb M, Zhao, Yiliang, Weiss, Sharon M, Duvall, Craig L
Format:	Journal Article
Language:	English
Published:	United States American Chemical Society 16-07-2014
Subjects:	Biosensing Techniques - methods Biosensors Carcinoma, Hepatocellular - genetics Carcinoma, Hepatocellular - metabolism Communication DNA - metabolism Drug Delivery Systems Gene therapy Humans Liver Neoplasms - genetics Liver Neoplasms - metabolism Mass Spectrometry MicroRNAs - administration & dosage MicroRNAs - antagonists & inhibitors MicroRNAs - metabolism Nanoparticles Nanoparticles - chemistry Nucleic Acid Hybridization Peptide Nucleic Acids - chemical synthesis Peptides Porosity Propylamines Silanes - chemistry Silicon Silicon - chemistry Tumor Cells, Cultured
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Summary:	Peptide 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1043-1802 1520-4812
DOI:	10.1021/bc5001092