MicroRNA delivery through nanoparticles

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Abstract

MicroRNAs (miRNAs) are attracting a growing interest in the scientific community due to their central role in the etiology of major diseases. On the other hand, nanoparticle carriers offer unprecedented opportunities for cell specific controlled delivery of miRNAs for therapeutic purposes. This review critically discusses the use of nanoparticles for the delivery of miRNA-based therapeutics in the treatment of cancer and neurodegenerative disorders and for tissue regeneration. A fresh perspective is presented on the design and characterization of nanocarriers to accelerate translation from basic research to clinical application of miRNA-nanoparticles. Main challenges in the engineering of miRNA-loaded nanoparticles are discussed, and key application examples are highlighted to underline their therapeutic potential for effective and personalized medicine.

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Most cited references 182

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Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs.

Lee P. Lim, Nelson C. Lau, Philip Garrett-Engele … (2005)

MicroRNAs (miRNAs) are a class of noncoding RNAs that post-transcriptionally regulate gene expression in plants and animals. To investigate the influence of miRNAs on transcript levels, we transfected miRNAs into human cells and used microarrays to examine changes in the messenger RNA profile. Here we show that delivering miR-124 causes the expression profile to shift towards that of brain, the organ in which miR-124 is preferentially expressed, whereas delivering miR-1 shifts the profile towards that of muscle, where miR-1 is preferentially expressed. In each case, about 100 messages were downregulated after 12 h. The 3' untranslated regions of these messages had a significant propensity to pair to the 5' region of the miRNA, as expected if many of these messages are the direct targets of the miRNAs. Our results suggest that metazoan miRNAs can reduce the levels of many of their target transcripts, not just the amount of protein deriving from these transcripts. Moreover, miR-1 and miR-124, and presumably other tissue-specific miRNAs, seem to downregulate a far greater number of targets than previously appreciated, thereby helping to define tissue-specific gene expression in humans.

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Prediction of mammalian microRNA targets.

Benjamin Lewis, I-hung Shih, Matthew W Jones-Rhoades … (2003)

MicroRNAs (miRNAs) can play important gene regulatory roles in nematodes, insects, and plants by basepairing to mRNAs to specify posttranscriptional repression of these messages. However, the mRNAs regulated by vertebrate miRNAs are all unknown. Here we predict more than 400 regulatory target genes for the conserved vertebrate miRNAs by identifying mRNAs with conserved pairing to the 5' region of the miRNA and evaluating the number and quality of these complementary sites. Rigorous tests using shuffled miRNA controls supported a majority of these predictions, with the fraction of false positives estimated at 31% for targets identified in human, mouse, and rat and 22% for targets identified in pufferfish as well as mammals. Eleven predicted targets (out of 15 tested) were supported experimentally using a HeLa cell reporter system. The predicted regulatory targets of mammalian miRNAs were enriched for genes involved in transcriptional regulation but also encompassed an unexpectedly broad range of other functions.

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Calculated absorption and scattering properties of gold nanoparticles of different size, shape, and composition: applications in biological imaging and biomedicine.

Prashant Jain, Kyeong Seok Lee, Ivan El-Sayed … (2006)

The selection of nanoparticles for achieving efficient contrast for biological and cell imaging applications, as well as for photothermal therapeutic applications, is based on the optical properties of the nanoparticles. We use Mie theory and discrete dipole approximation method to calculate absorption and scattering efficiencies and optical resonance wavelengths for three commonly used classes of nanoparticles: gold nanospheres, silica-gold nanoshells, and gold nanorods. The calculated spectra clearly reflect the well-known dependence of nanoparticle optical properties viz. the resonance wavelength, the extinction cross-section, and the ratio of scattering to absorption, on the nanoparticle dimensions. A systematic quantitative study of the various trends is presented. By increasing the size of gold nanospheres from 20 to 80 nm, the magnitude of extinction as well as the relative contribution of scattering to the extinction rapidly increases. Gold nanospheres in the size range commonly employed ( approximately 40 nm) show an absorption cross-section 5 orders higher than conventional absorbing dyes, while the magnitude of light scattering by 80-nm gold nanospheres is 5 orders higher than the light emission from strongly fluorescing dyes. The variation in the plasmon wavelength maximum of nanospheres, i.e., from approximately 520 to 550 nm, is however too limited to be useful for in vivo applications. Gold nanoshells are found to have optical cross-sections comparable to and even higher than the nanospheres. Additionally, their optical resonances lie favorably in the near-infrared region. The resonance wavelength can be rapidly increased by either increasing the total nanoshell size or increasing the ratio of the core-to-shell radius. The total extinction of nanoshells shows a linear dependence on their total size, however, it is independent of the core/shell radius ratio. The relative scattering contribution to the extinction can be rapidly increased by increasing the nanoshell size or decreasing the ratio of the core/shell radius. Gold nanorods show optical cross-sections comparable to nanospheres and nanoshells, however, at much smaller effective size. Their optical resonance can be linearly tuned across the near-infrared region by changing either the effective size or the aspect ratio of the nanorods. The total extinction as well as the relative scattering contribution increases rapidly with the effective size, however, they are independent of the aspect ratio. To compare the effectiveness of nanoparticles of different sizes for real biomedical applications, size-normalized optical cross-sections or per micron coefficients are calculated. Gold nanorods show per micron absorption and scattering coefficients that are an order of magnitude higher than those for nanoshells and nanospheres. While nanorods with a higher aspect ratio along with a smaller effective radius are the best photoabsorbing nanoparticles, the highest scattering contrast for imaging applications is obtained from nanorods of high aspect ratio with a larger effective radius.

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Author and article information

Contributors

Clara Mattu

Journal

Journal ID (nlm-ta): J Control Release

Journal ID (iso-abbrev): J Control Release

Title: Journal of Controlled Release

Publisher: Elsevier Science Publishers

ISSN (Print): 0168-3659

ISSN (Electronic): 1873-4995

Publication date PMC-release: 10 November 2019

Publication date (Print): 10 November 2019

Volume: 313

Pages: 80-95

Affiliations

[a ]Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Corso Duca Degli Abruzzi 24, 10129 Torino, Italy

[b ]Singapore-MIT Alliance for Research & Technology (SMART), BioSystems and Micromechanics (BioSyM), Singapore, Singapore ³

[c ]Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore ³

[d ]Singapore Immunology Network (SIgN), Agency for Science, Technology, and Research, Singapore, Singapore ³

[e ]Department of Mechanical Engineering, Massachusetts Institute of Technology, 500 Technology Square, Room NE47-321, Cambridge, MA, 02139, USA

[f ]Department of Biological Engineering, Massachusetts Institute of Technology, 500 Technology Square, Room NE47-321, Cambridge, MA, 02139, USA

[g ]Institute of Industrial Science, The University of Tokyo, Meguro-ku, Tokyo 153-8505, Japan ³

[h ]Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore, Singapore

Author notes

[* ]Corresponding authors. Clara.mattu@ 123456polito.it

[1]

These authors equally contributed as first authors.

[2]

These authors equally contributed as last authors.

[3]

Present addresses.

Article

Publisher ID: S0168-3659(19)30579-6

DOI: 10.1016/j.jconrel.2019.10.007

PMC ID: 6900258

PubMed ID: 31622695

SO-VID: 68e5f9d9-db8c-4995-88b5-14fda3783059

License:

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

History

Date received : 22 August 2019

Date revision received : 7 October 2019

Date accepted : 8 October 2019

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MicroRNA delivery through nanoparticles

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Most cited references 182

Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs.

Prediction of mammalian microRNA targets.

Calculated absorption and scattering properties of gold nanoparticles of different size, shape, and composition: applications in biological imaging and biomedicine.

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Contributors

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