Pentafluoropropionic Anhydride Functionalized PAMAM Dendrimer as miRNA Delivery Reagent

Yıl 2018, Cilt: 5 Sayı: 3, 1295 - 1302, 01.09.2018

Ali Oztuna Hasan Nazir

https://doi.org/10.18596/jotcsa.463855

Cited By: 4

Öz

Poly(amidoamine) (PAMAM) dendrimers are good
candidates for nucleic acid delivery with their well-defined characteristics.
MicroRNA (miRNA) mediated regulation of biological process are also active area
of investigation. Fibroblast cells, such as MRC-5, are one of the cell lines
used in biological researches due to their hard to transfect nature. In this two-staged
study, cystamine core G5 PAMAM dendrimers were synthesized and modified with pentafluoropropionic
anhydride (PA) and subsequently tested as miRNA delivery reagent on MRC-5
cells. Effect of fluorination against to naked G5 dendrimer over transfection
efficiency was also investigated by molecular docking and quantitative
structure-activity relationship (QSAR) calculations. Structural
characterization of the synthesized dendrimers was verified by spectroscopic
techniques. Gel retardation assay, particle size and transmission electron
microscopy results demonstrated polyplex formation ability of fluorinated
dendrimers with miRNA at nanoscale level. Zeta potential values indicated
non-aggregation and increased stability of the polyplexes. Prepared polyplexes
with fluorinated dendrimer showed over 90% cell viability and transfection
efficiency. In silico calculations confirmed the stable complexation with miRNA
and smooth penetration capability into the cell.

Anahtar Kelimeler

Cystamine-G5-PAMAM, pentafluoropropionic anhydride, miRNA, MRC-5

Kaynakça

• 1. Abbasi E, Aval SF, Akbarzadeh A, Milani M, Nasrabadi HT, Joo SW, Hanifehpour Y, Nejati-Koshki K, Pashaei-Asl R. Dendrimers: synthesis, applications, and properties. Nanoscale Res Lett. 2014;9(1):247.
• 2. Kaur D, Jain K, Mehra NK, Kesharwani P, Jain NK. A review on comparative study of PPI and PAMAM dendrimers. J Nanopart Res. 2016 Jun;18(6):146.
• 3. Kesharwani P, Banerjee S, Gupta U, Amin MCIM, Padhye S, Sarkar FH, Arun KI. PAMAM dendrimers as promising nanocarriers for RNAi therapeutics. Mater Today. 2015 Dec;18(10):565-72.
• 4. Oupický D, Li J. Bioreducible polycations in nucleic acid delivery: past, present, and future trends. Macromol Biosci. 2014 Jul;14(7):908-22.
• 5. Wang M, Liu H, Li L, Cheng Y. A fluorinated dendrimer achieves excellent gene transfection efficacy at extremely low nitrogen to phosphorus ratios. Nat Commun. 2014 Jan;5:3053.
• 6. Liu H, Wang Y, Wang M, Xiao J, Cheng Y. Fluorinated poly(propylenimine) dendrimers as gene vectors. Biomaterials. 2014 Jul;35(20):5407-13.
• 7. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004 Jan;116(2):281-97.
• 8. Christopher AF, Kaur RP, Kaur G, Kaur A, Gupta V, Bansal P. MicroRNA therapeutics: Discovering novel targets and developing specific therapy. Perspect Clin Res. 2016 Apr-Jun;7(2):68-74.
• 9. Gary D J, Puri N, Won YY. Polymer-based siRNA delivery: perspectives on the fundamental and phenomenological distinctions from polymer-based DNA delivery. J Control Release. 2007 Aug;121(1-2):64-73.
• 10. Wang M, Cheng Y. Structure-activity relationships of fluorinated dendrimers in DNA and siRNA delivery. Acta Biomater. 2016 Dec;46:204-10.
• 11. Liu H, Chang H, Lv J, Jiang C, Li Z, Wang F, Wang H, Wang M, Liu C, Wang X, et al. Screening of efficient siRNA carriers in a library of surface-engineered dendrimers. Sci Rep. 2016 Apr;28,6:25069.
• 12. Tomalia DA, Huang B, Swanson DR, Brothers II HM, Klimash JW. Structure control within poly(amidoamine) dendrimers: size, shape and regio-chemical mimicry of globular proteins. Tetrahedron. 2003 May;59(22):3799-813.
• 13. Oztuna A, Nazir H. In-vitro transfection potential of fluorinated G5 PAMAM dendrimers for miRNA delivery to MRC-5 cells. Eur Res J. 2018 Apr;4(2):92-100.
• 14. Duhovny D, Nussinov R, Wolfson HJ. Efficient Unbound Docking of Rigid Molecules. In: Guigó R, Gusfield D, editors. Algorithms in Bioinformatics. WABI 2002, LNCS 2452, Springer-Verlag, Berlin, Heidelberg, p. 185-200. Available from: https://link.springer.com/chapter/10.1007/3-540-45784-4_14
• 15. Schneidman-Duhovny D, Inbar Y, Nussinov R, Wolfson HJ. PatchDock and SymmDock: servers for rigid and symmetric docking. Nucleic Acids Res. 2005 Jul;33(2):W363-7.
• 16. Andrusier N, Nussinov R, Wolfson HJ. FireDock: fast interaction refinement in molecular docking. Proteins. 2007 Oct;69(1):139-59.
• 17. Mashiach E, Schneidman-Duhovny D, Andrusier N, Nussinov R, Wolfson HJ. FireDock: a web server for fast interaction refinement in molecular docking. Nucleic Acids Res. 2008 Jul;36(2):W229-32.
• 18. Puzyn T, Leszczynska D, Leszczynski J. Toward the development of “Nano‐QSARs”: Advances and challenges. Small. 2009 Nov;5(22):2494-509.
• 19. Gao H, Shi W, Freund LB. Mechanics of receptor-mediated endocytosis. Proc Natl Acad Sci USA. 2005 Jul;102(27):9469-74.
• 20. Kim SH, Jeong JH, Lee SH, Kim SW, Park TG. PEG conjugated VEGF siRNA for anti-angiogenic gene therapy. J Control Release. 2006 Nov;116(2):123-29.
• 21. Li W, Szoka FC Jr. Lipid-based nanoparticles for nucleic acid delivery. Pharm Res. 2007 Mar;24(3):438-49.
• 22. Dobrovolskaia MA, Patri AK, Simak J, Hall JB, Semberova J, De Paoli Lacerda SH, McNeil SE. Nanoparticle size and surface charge determine effects of PAMAM dendrimers on human platelets in vitro. Mol Pharm. 2012 Mar;9(3):382-93.
• 23. Ferenc M, Pedziwiatr-Werbicka E, Nowak KE, Klajnert B, Majoral JP, Bryszewska M. Phosphorus dendrimers as carriers of siRNA-characterisation of dendriplexes. Molecules. 2013 Apr;18(4):4451-66.