Porous silicon-cell penetrating peptide hybrid nanocarrier for intracellular delivery of oligonucleotides

Molecular Pharmaceutics
Jussi RytkönenAle Närvänen

Abstract

The largest obstacle to the use of oligonucleotides as therapeutic agents is the delivery of these large and negatively charged biomolecules through cell membranes into intracellular space. Mesoporous silicon (PSi) is widely recognized as a potential material for drug delivery purposes due to its several beneficial features like large surface area and pore volume, high loading capacity, biocompatibility, and biodegradability. In the present study, PSi nanoparticles stabilized by thermal oxidation or thermal carbonization and subsequently modified by grafting aminosilanes on the surface are utilized as an oligonucleotide carrier. Splice correcting oligonucleotides (SCOs), a model oligonucleotide drug, were loaded into the positively charged PSi nanoparticles with a loading degree as high as 14.3% (w/w). Rapid loading was achieved by electrostatic interactions, with the loading efficiencies reaching 100% within 5 min. The nanoparticles were shown to deliver and release SCOs, in its biologically active form, inside cells when formulated together with cell penetrating peptides (CPP). The biological effect was monitored with splice correction assay and confocal microscopy utilizing HeLa pLuc 705 cells. Furthermore, the use of PSi ca...Continue Reading

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Aug 22, 2015·Nanomedicine·Morteza Hasanzadeh KafshgariFrances J Harding
Feb 19, 2015·Therapeutic Delivery·Timothy J Barnes, Clive A Prestidge
Mar 2, 2017·Pharmaceutical Patent Analyst·Paulina A Kulyavtsev, Roxanne P Spencer
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Jan 11, 2020·ACS Applied Materials & Interfaces·Wujun XuVesa-Pekka Lehto

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