Combinatorial Delivery of miRNA‐Nanoparticle Conjugates in Human Adipose Stem Cells for Amplified Osteogenesis. Issue 50 (14th November 2019)

• Record Type: Journal Article
• Authors: Abu‐Laban, Mohammad; Hamal, Prakash; Arrizabalaga, Julien H.; Forghani, Anoosha; Dikkumbura, Asela S.; Kumal, Raju R.; Haber, Louis H.; Hayes, Daniel J.
• Is Part Of: Small. Volume 15:Issue 50(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-11-14
• Subjects: gold -- microRNA -- nanoparticles -- retro‐Diels–Alder -- sequential -- silver; Nanotechnology -- Periodicals; Nanoparticles -- Periodicals; Microtechnology -- Periodicals; 620.5
• DOI: 10.1002/smll.201902864
• Languages: English
• ISSNs: 1613-6810

Abstract

Abstract: It is becoming more apparent in tissue engineering applications that fine temporal control of multiple therapeutics is desirable to modulate progenitor cell fate and function. Herein, the independent temporal control of the co‐delivery of miR‐148b and miR‐21 mimic plasmonic nanoparticle conjugates to induce osteogenic differentiation of human adipose stem cells (hASCs), in a de novo fashion, is described. By applying a thermally labile retro‐Diels–Alder caging and linkage chemistry, these miRNAs can be triggered to de‐cage serially with discrete control of activation times. The method relies on illumination of the nanoparticles at their resonant wavelengths to generate sufficient local heating and trigger the untethering of the Diels–Alder cycloadduct. Characterization of the photothermal release using fluorophore‐tagged miRNA mimics in vitro is carried out with fluorescence measurements, second harmonic generation, and confocal imaging. Osteogenesis of hASCs from the sequential co‐delivery of miR‐21 and miR‐148b mimics is assessed using xylenol orange and alizarin red staining of deposited minerals, and quantitative polymerase chain reaction for gene expression of osteogenic markers. The results demonstrate that sequential miRNA mimic activation results in upregulation of osteogenic markers and mineralization relative to miR‐148b alone, and co‐activation of miR‐148b and miR‐21 at the same time. Abstract : By coupling two separate miRNA mimics to gold and silver nanoparticles, multiplexed delivery to induce and enhance osteogenic differentiation in hASCs is achieved. Utilizing the thermally labile properties of retro‐Diels‐Alder linkage chemistry, the plasmon resonance of the nanoparticles produces significant localized heat to trigger sequential release upon irradiation.