Combinatorial Delivery of miRNA-Nanoparticle Conjugates in Human Adipose Stem Cells for Amplified Osteogenesis

Mohammad Abu-Laban, Prakash Hamal, Julien H. Arrizabalaga, Anoosha Forghani, Asela S. Dikkumbura, Raju R. Kumal, Louis H. Haber, Daniel J. Hayes

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number1902864
JournalSmall
Volume15
Issue number50
DOIs
StatePublished - Dec 1 2019

Fingerprint

Stem cells
MicroRNAs
Osteogenesis
Nanoparticles
Stem Cells
Chemical activation
Alizarin
Fluorophores
Polymerase chain reaction
Tissue Engineering
Harmonic generation
Lighting
Tissue engineering
Gene expression
Heating
Minerals
Up-Regulation
Fluorescence
Staining and Labeling
Gene Expression

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biomaterials
  • Chemistry(all)
  • Materials Science(all)

Cite this

Abu-Laban, M., Hamal, P., Arrizabalaga, J. H., Forghani, A., Dikkumbura, A. S., Kumal, R. R., ... Hayes, D. J. (2019). Combinatorial Delivery of miRNA-Nanoparticle Conjugates in Human Adipose Stem Cells for Amplified Osteogenesis. Small, 15(50), [1902864]. https://doi.org/10.1002/smll.201902864
Abu-Laban, Mohammad ; Hamal, Prakash ; Arrizabalaga, Julien H. ; Forghani, Anoosha ; Dikkumbura, Asela S. ; Kumal, Raju R. ; Haber, Louis H. ; Hayes, Daniel J. / Combinatorial Delivery of miRNA-Nanoparticle Conjugates in Human Adipose Stem Cells for Amplified Osteogenesis. In: Small. 2019 ; Vol. 15, No. 50.
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Abu-Laban, M, Hamal, P, Arrizabalaga, JH, Forghani, A, Dikkumbura, AS, Kumal, RR, Haber, LH & Hayes, DJ 2019, 'Combinatorial Delivery of miRNA-Nanoparticle Conjugates in Human Adipose Stem Cells for Amplified Osteogenesis', Small, vol. 15, no. 50, 1902864. https://doi.org/10.1002/smll.201902864

Combinatorial Delivery of miRNA-Nanoparticle Conjugates in Human Adipose Stem Cells for Amplified Osteogenesis. / Abu-Laban, Mohammad; Hamal, Prakash; Arrizabalaga, Julien H.; Forghani, Anoosha; Dikkumbura, Asela S.; Kumal, Raju R.; Haber, Louis H.; Hayes, Daniel J.

In: Small, Vol. 15, No. 50, 1902864, 01.12.2019.

Research output: Contribution to journalArticle

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T1 - Combinatorial Delivery of miRNA-Nanoparticle Conjugates in Human Adipose Stem Cells for Amplified Osteogenesis

AU - Abu-Laban, Mohammad

AU - Hamal, Prakash

AU - Arrizabalaga, Julien H.

AU - Forghani, Anoosha

AU - Dikkumbura, Asela S.

AU - Kumal, Raju R.

AU - Haber, Louis H.

AU - Hayes, Daniel J.

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Y1 - 2019/12/1

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AB - 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.

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Abu-Laban M, Hamal P, Arrizabalaga JH, Forghani A, Dikkumbura AS, Kumal RR et al. Combinatorial Delivery of miRNA-Nanoparticle Conjugates in Human Adipose Stem Cells for Amplified Osteogenesis. Small. 2019 Dec 1;15(50). 1902864. https://doi.org/10.1002/smll.201902864