The field of nanomaterials for drug delivery utilizing light-mediated oligonucleotide release is continuing to develop. We have investigated the controllable, light activated release of oligonucleotides from colloidal gold nanoparticle (AuNP) surfaces using ultraviolet (UV) light. This drug delivery technique is achieved by utilizing a nitrobenzyl photo-cleavable (NBPC) linker that connects to the surface of an AuNP on one side and a miRNA molecule on the other side. The photocleaving release of miRNA from the AuNP is monitored in real-time using the surface-sensitive nonlinear optical technique of second harmonic generation (SHG) as a function of the irradiation time, power, and wavelength of the photocleaving UV laser. Quantification measurements, including fluorimetry, extinction spectroscopy, and zeta potential measurements confirm these SHG results on the photocleaving dynamics. As a second study, the use of silver nanoparticles (AgNPs) are used to further enhance the controlled release of oligonucleotides several fold due to the plasmon enhancement from AgNPs which is on resonance with the PC linker. We have also extended this concept for photocleaving to the near-infrared (NIR) region, using gold-silver-gold core shell nanoparticles (Au-Ag-Au NPs) as a drug delivery vector for siRNAs as potential therapy for a variety of dermal cancers. These Au-Ag-Au NPs have a plasmon peak near 800 nm, a highly effective wavelength for dermal infiltration. We have studied the photothermal release of this siRNA complex through the analogue of a similar test case miRNA, utilizing the fluorophore-miRNA conjugated with a retro Diels-Alder linker. These results are compared to corresponding measurements on miRNA-functionalized gold nanorods which have a longitudinal plasmon resonance in the NIR. Additional work will include a brief cell study of miRNA uptake, as released from the Au-Ag-Au NPs compared to AuNPs. This particular complex is to be specifically applied to the research of therapies for HIV-associated malignancies like Kaposi’s Sarcoma through the use of siRNAs specific to the downregulation of extracellular matrix metalloproteinase and LYVE-1 which are associated with angiogenesis, metastasis, migration, and invasion.

Second harmonic generation studies on plasmonic nanoparticles for light-mediated drug delivery

251st National Meeting (2016)

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