Abstract
Polyamidoamine dendrimers (PAMAM) form positively charged nanoparticles that function as nonviral delivery vectors for gene therapy. They protect nucleic acids from enzymatic degradation and facilitate endocytosis and endosomal escape. In this chapter, we describe the preparation and in vitro evaluation of small interfering RNA (siRNA)-PAMAM dendrimers. The physicochemical properties of the designed formulations were evaluated by size and zeta potential assessment and atomic force microscopy (AFM). The binding and release of the siRNA molecules from the PAMAM dendrimers were also assessed. Visualization and quantitative analysis of the siRNA-PAMAM dendrimers in live cells were analyzed by fluorescence microscopy and flow cytometry, respectively. Improving siRNA delivery to human cells through PAMAM dendrimers should accelerate the clinical applications of RNA interference.
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References
Ayatollahi S, Salmasi Z, Hashemi M, Askarian S, Oskuee RK, Abnous K, Ramezani M (2017) Aptamer-targeted delivery of Bcl-xL shRNA using alkyl modified PAMAM dendrimers into lung cancer cells. Int J Biochem Cell Biol 92:210–217
Gu J, Fang X, Hao J, Sha X (2015) Reversal of P-glycoprotein-mediated multidrug resistance by CD44 antibody-targeted nanocomplexes for short hairpin RNA-encoding plasmid DNA delivery. Biomaterials 45:99–114
Chang PK, Prestidge CA, Bremmell KE (2017) Interfacial analysis of siRNA complexes with poly-ethylenimine (PEI) or PAMAM dendrimers in gene delivery. Colloids Surf B: Biointerfaces 158:370–378
Abedi-Gaballu F, Dehghan G, Ghaffari M, Yekta R, Abbaspour-Ravasjani S, Baradaran B, Dolatabadi JEN, Hamblin MR (2018) PAMAM dendrimers as efficient drug and gene delivery nanosystems for cancer therapy. Appl Mater Today 12:177–190
Ghaffari M, Dehghan G, Abedi-Gaballu F, Kashanian S, Baradaran B, Ezzati Nazhad Dolatabadi J, Losic D (2018) Surface functionalized dendrimers as controlled-release delivery nanosystems for tumor targeting. Eur J Pharm Sci 122:11–330
Ezzati Nazhad Dolatabadi J, Omidi Y (2016) Solid lipid-based nanocarriers as efficient targeted drug and gene delivery systems. TrAC Trends Anal Chem 77:100–108
Ezzati Nazhad Dolatabadi J, Omidi Y, Losic D (2011) Carbon nanotubes as an advanced drug and gene delivery nanosystem. Curr Nanosci 7:297–314
Pandi P et al (2018) Dendrimer as a new potential carrier for topical delivery of siRNA: comparative study of dendriplex vs. lipoplex for delivery of TNF-α siRNA. Int J Pharm 550(1–2):240–250
Perez A, Romero E, Morilla M (2009) Ethylendiamine core PAMAM dendrimers/siRNA complexes as in vitro silencing agents. Int J Pharm 380(1–2):189–200
Wang Y, Fang J, Cheng D, Wang Y, Shuai X (2014) A pH-sensitive micelle for codelivery of siRNA and doxorubicin to hepatoma cells. Polymer 55:3217–3226
Zhou J, Neff CP, Liu X, Zhang J, Li H, Smith DD, Swiderski P, Aboellail T, Huang Y, Du Q, Liang Z, Peng L, Akkina R, Rossi JJ (2011) Systemic administration of combinatorial dsiRNAs via nanoparticles efficiently suppresses HIV-1 infection in humanized mice. Mol Ther 19:2228–2238
Zhang Y, Wang Z, Gemeinhart RA (2013) Progress in microRNA delivery. J Control Release 172:962–974
Shan Y, Luo T, Peng C, Sheng R, Cao A, Cao X, Shen M, Guo R, Tomás H, Shi X (2012) Gene delivery using dendrimer-entrapped gold nanoparticles as nonviral vectors. Biomaterials 33:3025–3035
Tariq I, Pinnapireddy SR, Duse L, Ali MY, Ali S, Amin MU, Goergen N, Jedelská J, Schäfer J, Bakowsky U (2018) Lipodendriplexes: A promising nanocarrier for enhanced gene delivery with minimal cytotoxicity. Eur J Pharm Biopharm 135:72–82
Ma D, Lin QM, Zhang LM, Liang YY, Xue W (2014) A star-shaped porphyrin-arginine functionalized poly(L-lysine) copolymer for photo-enhanced drug and gene co-delivery. Biomaterials 35:4357–4367
Zarebkohan A, Najafi F, Moghimi HR, Hemmati M, Deevband MR, Kazemi B (2015) Synthesis and characterization of a PAMAM dendrimer nanocarrier functionalized by SRL peptide for targeted gene delivery to the brain. Eur J Pharm Sci 12:19–30
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Kheiriabad, S., Ghaffari, M., Dolatabadi, J.E.N., Hamblin, M.R. (2020). PAMAM Dendrimers as a Delivery System for Small Interfering RNA. In: Sioud, M. (eds) RNA Interference and CRISPR Technologies. Methods in Molecular Biology, vol 2115. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0290-4_5
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DOI: https://doi.org/10.1007/978-1-0716-0290-4_5
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