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RNA Delivery via DNA-Inspired Janus Base Nanotubes for Extracellular Matrix Penetration

Published online by Cambridge University Press:  24 January 2020

Ian Sands
Affiliation:
Department of Engineering, University of Connecticut, Storrs, CT.
Jinhyung Lee
Affiliation:
Department of Engineering, University of Connecticut, Storrs, CT.
Wuxia Zhang
Affiliation:
Department of Engineering, University of Connecticut, Storrs, CT.
Yupeng Chen*
Affiliation:
Department of Engineering, University of Connecticut, Storrs, CT.
*
*Yupeng.chen@uconn.edu
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Abstract

RNA delivery into deep tissues with dense extracellular matrix (ECM) has been challenging. For example, cartilage is a major barrier for RNA and drug delivery due to its avascular structure, low cell density and strong negative surface charge. Cartilage ECM is comprised of collagens, proteoglycans, and various other noncollagneous proteins with a spacing of 20nm. Conventional nanoparticles are usually spherical with a diameter larger than 50-60nm (after cargo loading). Therefore, they presented limited success for RNA delivery into cartilage. Here, we developed Janus base nanotubes (JBNTs, self-assembled nanotubes inspired from DNA base pairs) to assemble with small RNAs to form nano-rod delivery vehicles (termed as “Nanopieces”). Nanopieces have a diameter of ∼20nm (smallest delivery vehicles after cargo loading) and a length of ∼100nm. They present a novel breakthrough in ECM penetration due to the reduced size and adjustable characteristics to encourage ECM and intracellular penetration.

Type
Articles
Copyright
Copyright © Materials Research Society 2020

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References

References:

Agrawal, N, Dasaradhi, PVN, Mohmmed, A, Malhotra, P, Bhatnagar, RK, Mukherjee, SK, RNA interference: biology, mechanism, and applications. Microbiol Mol Biol Rev. 2003;67(4):657-85.CrossRefGoogle ScholarPubMed
Lotz, MK, Kraus, VB. New developments in osteoarthritis. Posttraumatic osteoarthritis pathogenesis and pharmacological treatment options. Arthritis Res Ther. 2010;12(3):211.CrossRefGoogle ScholarPubMed
Trozilli, P. A., ArduinoJ,M. J,M., Gregory, J.D. & Bansal, M.Effect of proteoglycan removal on solute mobility in articular cartilage. J. Biomech. 1997; 30, 895-902.CrossRefGoogle Scholar
Chen, Y, Song, S, Yan, Z, Fenniri, H, Webster, TJ. Self-assembled rosette nanotubes encapsulate and slowly release dexamethasone. Int J Nanomedicine. 2011;6:1035-44.Google ScholarPubMed
Moralez, JG, Raez, J, Yamazaki, T, Motkuri, RK, Kovalenko, A, Fenniri, H. Helical Rosette Nanotubes with Tunable Stability and Hierarchy. Journal of the American Chemical Society. 2005;127(23):8307-9.CrossRefGoogle ScholarPubMed
Song, S, Chen, Y, Yan, Z, Fenniri, H, Webster, TJ. Self-assembled rosette nanotubes for incorporating hydrophobic drugs in physiological environments. International journal of nanomedicine. 2011;6:101-7.Google ScholarPubMed
Zhang, L, Chen, Y, Rodriguez, J, Fenniri, H, Webster, TJ. Biomimetic helical rosette nanotubes and nanocrystalline hydroxyapatite coatings on titanium for improving orthopedic implants. International journal of nanomedicine. 2008;3(3):323-33.Google ScholarPubMed
Chen, Y, Bilgen, B, Pareta, RA, Myles, AJ, Fenniri, H, Ciombor, DM, et al. Self-Assembled Rosette Nanotube/Hydrogel Composites for Cartilage Tissue Engineering. Tissue Engineering Part C: Methods. 2010;16(6):1233-43.CrossRefGoogle ScholarPubMed
Journeay, WS, Suri, SS, Moralez, JG, Fenniri, H, Singh, B. Rosette nanotubes show low acute pulmonary toxicity in vivo. International journal of nanomedicine. 2008;3(3):373-83.Google ScholarPubMed
Zhang, L, Rakotondradany, F, Myles, AJ, Fenniri, H, Webster, TJ. Arginine-glycine-aspartic acid modified rosette nanotube–hydrogel composites for bone tissue engineering. Biomaterials. 2009;30(7):1309-20.CrossRefGoogle ScholarPubMed
Hanemann, T, Szabo, DV. Polymer-Nanoparticle Composites: From Synthesis to Modern Applications. Materials. 2010;3(6):3468-517. doi: 10.3390/ma3063468.CrossRefGoogle Scholar
Aryal, S, Pilla, S, Gong, S. Multifunctional nano-micelles formed by amphiphilic gold-polycaprolactone-methoxy poly(ethylene glycol) (Au-PCL-MPEG) nanoparticles for potential drug delivery applications. J Nanosci Nanotechnol. 2009;9(10):5701-8.CrossRefGoogle ScholarPubMed
Mu, H, Holm, R, Mullertz, A. Lipid-based formulations for oral administration of poorly water-soluble drugs. Int J Pharm. 2013;453(1):215-24. doi: 10.1016/j.ijpharm.2013.03.054.CrossRefGoogle ScholarPubMed
Zhang, F, Lin, Y-A, Kannan, S, Kannan, RM. Targeting specific cells in the brain with nanomedicines for CNS therapies. Journal of Controlled Release. 2016;240:212-26.CrossRefGoogle ScholarPubMed
Chu, DSH, Schellinger, JG, Bocek, MJ, Johnson, RN, Pun, SH. Optimization of Tet1 ligand density in HPMA-co-oligolysine copolymers for targeted neuronal gene delivery. Biomaterials. 2013;34(37):9632-7.CrossRefGoogle ScholarPubMed
da Fonseca, AC, Badie, B. Microglia and macrophages in malignant gliomas: recent discoveries and implications for promising therapies. Clin Dev Immunol. 2013;2013:264124.Google ScholarPubMed
Suk, JS, Xu, Q, Kim, N, Hanes, J, Ensign, LM. PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. Adv Drug Deliv Rev. 2016;99(Pt A):28-51CrossRefGoogle ScholarPubMed
Abuchowski, A, McCoy, JR, Palczuk, NC, van Es, T, Davis, FF. Effect of covalent attachment of polyethylene glycol on immunogenicity and circulating life of bovine liver catalase. J Biol Chem. 1977;252(11):3582-6.Google ScholarPubMed