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Sol–gel derived silica/polyethylene glycol hybrids as potential oligonucleotide vectors

Published online by Cambridge University Press:  28 November 2019

Derya Kapusuz*
Affiliation:
Department of Metallurgical and Materials Engineering, Gaziantep University, Gaziantep 27310, Turkey
*
a)Address all correspondence to this author. e-mail: dekapusuz@gmail.com
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Abstract

Until recently, mesoporous silica (MPS) particles have been successfully used in various biomedical applications including drug delivery. In the past decades, the research on MPS shifted sharply to gene delivery owing to its biocompatible, mesoporous structure that allows for loading oligonucleotides, shielding in the bloodstream, and delivering them to patient cells’ cytoplasm to stop cells’ genetic transcription. Until now, researchers faced several unique challenges and MPS, as oligonucleotide vectors, could not reach the clinical stage. In this study, material-related challenges were endeavored to overcome by a combined particle synthesis/oligo-loading strategy. DNA-encapsulated silica/polyethylene glycol (PEG) hybrid xerogels were synthesized at one step, via sol–gel technique. The xerogels were grinded into particles and characterized by X-ray diffraction, scanning electron microscopy, ultraviolet–visible spectroscopy, Fourier transform infrared spectroscopy, and gas adsorption analysis. The results demonstrated that uniform oligo-loaded silica/PEG hybrid xerogels could be synthesized without surface modification. Oligonucleotides were encapsulated inside the whole porous network, rather than attached only to particle surfaces as such in the conventional route. The results showed that PEG incorporation led to formation of monolithic xerogels, which could be grinded into spherical particles (557 ± 110 nm) with well-defined edges. Due to grinding, PEG chains were present both in the interior and on the surface of the particles. 10% PEG incorporation into silica precursor (tetraethyl orthosilicate) increased the resistance of DNA-encapsulated silica against protein degradation. In the overall sol–gel-derived silica/PEG hybrid materials were revealed as potential candidates for gene delivery applications such as RNA interference therapies.

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Article
Copyright
Copyright © Materials Research Society 2019 

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References

Cheng, S.H., Lee, C.H., Chen, M.C., Souris, J.S., Tseng, F.G., Yang, C.S., Mou, C.Y., Chen, C.T., and Lo, L.W.: Tri-functionalization of mesoporous silica nanoparticles for comprehensive cancer theranostics—the trio of imaging, targeting and therapy. J. Mater. Chem. 20, 6149 (2010).CrossRefGoogle Scholar
Slowing, I., Trewyn, B.G., and Lin, V.S.Y.: Effect of surface functionalization of MCM-41-type mesoporous silica nanoparticles on the endocytosis by human cancer cells. J. Am. Chem. Soc. 128, 14792 (2006).CrossRefGoogle ScholarPubMed
Shi, X., Wang, Y., Ren, L., Zhao, N., Gong, Y., and Wang, D.A.: Novel mesoporous silica-based antibiotic releasing scaffold for bone repair. Acta Biomater. 5, 1697 (2009).CrossRefGoogle ScholarPubMed
Kim, J., Kim, H.S., Lee, N., Kim, T., Kim, H., Yu, T., Song, I.C., Moon, W.K., and Hyeon, T.: Multifunctional uniform nanoparticles composed of a magnetite nanocrystal core and a mesoporous silica shell for magnetic resonance and fluorescence imaging and for drug delivery. Angew. Chem. 120, 8566 (2008).CrossRefGoogle Scholar
Stöber, W., Fink, A., and Bohn, E.: Controlled growth of monodisperse silica spheres in the micron size range. J. Colloid Interface Sci. 26, 62 (1968).CrossRefGoogle Scholar
Yanagisawa, T., Shimizu, T., Kuroda, K., and Kato, C.: The preparation of alkyltriinethylaininonium–kaneinite complexes and their conversion to microporous materials. Bull. Chem. Soc. Jpn. 63, 988 (1990).CrossRefGoogle Scholar
Vallet-Regí, M., Colilla, M., Izquierdo-Barba, I., and Manzano, M.: Mesoporous silica nanoparticles for drug delivery: Current insights. Molecules 23, 308 (2017).10.3390/molecules23010047CrossRefGoogle ScholarPubMed
Zhang, J. and Cai, K.: Integration of polymers in the pore space of mesoporous nanocarriers for drug delivery. J. Mater. Chem. B 5, 8891 (2017).10.1039/C7TB02559ACrossRefGoogle ScholarPubMed
Shin, H.S., Hwang, Y.K., and Huh, S.: Facile preparation of ultra-large pore mesoporous silica nanoparticles and their application to the encapsulation of large guest molecules. ACS Appl. Mater. Interfaces 6, 1740 (2014).CrossRefGoogle ScholarPubMed
Jafari, S., Derakhshankhah, H., Alaei, L., Fattahi, A., Varnamkhasti, B.S., and Saboury, A.A.: Mesoporous silica nanoparticles for therapeutic/diagnostic applications. Biomed. Pharmacother. 109, 1100 (2019).CrossRefGoogle ScholarPubMed
Xia, T., Kovochich, M., Liong, M., Meng, H., Kabehie, S., George, S., Zink, J.I., and Nel, A.E.: Polyethyleneimine coating enhances the cellular uptake of mesoporous silica nanoparticles and allows safe delivery of siRNA and DNA constructs. ACS Nano 3, 3273 (2009).CrossRefGoogle ScholarPubMed
Torney, F., Trewyn, B.G., Lin, V.S-Y., and Wang, K.: Mesoporous silica nanoparticles deliver DNA and chemicals into plants. Nat. Nanotechnol. 2, 295 (2007).CrossRefGoogle ScholarPubMed
Baeza, A., Colilla, M., and Vallet-Regí, M.: Advances in mesoporous silica nanoparticles for targeted stimuli-responsive drug delivery. Expert Opin. Drug Deliv. 12, 319 (2015).CrossRefGoogle ScholarPubMed
Anderson, B.R., Muramatsu, H., Jha, B.K., Silverman, R.H., Weissman, D., and Kariko, K.: Nucleoside modifications in RNA limit activation of 2′-5′-oligoadenylate synthetase and increase resistance to cleavage by RNase L. Nucleic Acids Res. 39, 9329 (2011).10.1093/nar/gkr586CrossRefGoogle ScholarPubMed
Li, L., Hu, X., Zhang, M., Ma, S., Yu, F., Zhao, S., Liu, N., Wang, Z., Wang, Y., Guan, H., Pan, X., Gao, Y., Zhang, Y., Liu, Y., Yang, Y., Tang, X., Li, M., Liu, C., Li, Z., and Mei, X.: Dual tumor-targeting nanocarrier system for siRNA delivery based on pRNA and modified chitosan. Mol. Ther.-Nucleic Acids 8, 169 (2017).CrossRefGoogle ScholarPubMed
Na, H-K., Kim, M-H., Park, K., Ryoo, S-R., Lee, K.E., Jeon, H., Ryoo, R., Hyeon, C., and Min, D-H.: Efficient functional delivery of siRNA using mesoporous silica nanoparticles with ultralarge pores. Small 8, 1752 (2012).CrossRefGoogle ScholarPubMed
He, Q., Zhang, J., Shi, J., Zhu, Z., Zhang, L., Bu, W., Guo, L., and Chen, Y.: The effect of PEGylation of mesoporous silica nanoparticles on nonspecific binding of serum proteins and cellular responses. Biomaterials 31, 1085 (2010).CrossRefGoogle ScholarPubMed
Shehata Draz, M., Amanda Fang, B., Zhang, P., Hu, Z., Gu, S., Weng, K.C., Gray, J.W., and Frank Chen, F.: Nanoparticle-mediated systemic delivery of siRNA for treatment of cancers and viral infections. Theranostics 4, 872 (2014).CrossRefGoogle Scholar
Wang, M., Li, X., Ma, Y., and Gu, H.: Endosomal escape kinetics of mesoporous silica-based system for efficient siRNA delivery. Int. J. Pharm. 448, 51 (2013).CrossRefGoogle ScholarPubMed
Kapusuz, D. and Durucan, C.: Synthesis of DNA-encapsulated silica elaborated by sol–gel routes. J. Mater. Res. 28, 175 (2013).CrossRefGoogle Scholar
Kapusuz, D. and Durucan, C.: Exploring encapsulation mechanism of DNA and mononucleotides in sol–gel derived silica. J. Biomater. Appl. 32, 114 (2017).CrossRefGoogle ScholarPubMed
Brinker, C.J. and Scherer, G.W.: Sol–Gel Science: The Physics and Chemistry of Sol–Gel Processing (Academic Press, Boston, 1990).Google Scholar
Bhatia, R.B., Brinker, C.J., Gupta, A.K., and Singh, A.K.: Aqueous sol–gel process for protein encapsulation. Chem. Mater. 12, 2434 (2000).CrossRefGoogle Scholar
Pierre, A.C.: The sol–gel encapsulation of enzymes. Biocatal. Biotransform. 22, 145 (2004).CrossRefGoogle Scholar
Reátegui, E., Kasinkas, L., Kniesz, K., Lefebvre, M.A., and Aksan, A.: Silica–PEG gel immobilization of mammalian cells. J. Mater. Chem. B 2, 7440 (2014).CrossRefGoogle ScholarPubMed
Kwon, K.D., Vadillo-Rodriguez, V., Logan, B.E., and Kubicki, J.D.: Interactions of biopolymers with silica surfaces: Force measurements and electronic structure calculation studies. Geochim. Cosmochim. Acta 70, 3803 (2006).CrossRefGoogle Scholar
Fujiwara, M., Yamamoto, F., Okamoto, K., Shiokawa, K., and Nomura, R.: Adsorption of duplex DNA on mesoporous silicas: Possibility of inclusion of DNA into their mesopores. Anal. Chem. 77, 8138 (2005).CrossRefGoogle ScholarPubMed
Sharma, S., Johnson, R.W., and Desai, T.A.: XPS and AFM analysis of antifouling PEG interfaces for microfabricated silicon biosensors. Biosens. Bioelectron. 20, 227 (2004).CrossRefGoogle ScholarPubMed
Gross, T., Ramm, M., Sonntag, H., Unger, W., Weijers, H.M., and Adem, E.H.: An XPS analysis of different SiO2 modifications employing a C 1s as well as an Au 4f 7/2 static charge reference. Surf. Interface Anal. 18, 59 (1992).CrossRefGoogle Scholar
Stephenson, D.A. and Binkowski, N.J.: X-ray photoelectron spectroscopy of silica in theory and experiment. J. Non-Cryst. Solids 22, 399 (1976).CrossRefGoogle Scholar
Beganskienė, A., Beganskienė, A., Sirutkaitis, V., Kurtinaitienė, M., Juškėnas, R., and Kareiva, A.: FTIR, TEM, and NMR investigations of Stöber silica nanoparticles. Mater. Sci. Eng. C 10, 287 (2004).Google Scholar
Matos, M.C., Ilharco, L.M., and Almeida, R.M.: The evolution of TEOS to silica gel and glass by vibrational spectroscopy. J. Non-Cryst. Solids 147–148, 232 (1992).CrossRefGoogle Scholar
Nariyal, B.B.R.K. and Kothari, P.: FTIR measurements of SiO2 glass prepared by sol–gel technique. Chem. Sci. Trans. 3, 1064 (2014).Google Scholar
Rubio, F., Rubio, J., and Oteo, J.L.: A FT-IR study of the hydrolysis of tetraethylorthosilicate (TEOS). Spectrosc. Lett. 31, 199 (1998).CrossRefGoogle Scholar
Akbari, A., Yegani, R., and Pourabbas, B.: Synthesis of poly(ethylene glycol) (PEG) grafted silica nanoparticles with a minimum adhesion of proteins via one-pot one-step method. Colloids Surf., A 484, 206 (2015).CrossRefGoogle Scholar
Chu, P-Y. and Clark, D.E.: Infrared spectroscopy of silica sols–effects of water concentration, catalyst, and aging. Spectrosc. Lett. 25, 201 (1992).CrossRefGoogle Scholar
Lesot, P., Chapuis, S., Bayle, J.P., Rault, J., Lafontaine, E., Campero, A., and Judeinstein, P.: Structural–dynamical relationship in silica PEG hybrid gels. J. Mater. Chem. 8, 147 (1998).CrossRefGoogle Scholar
Vong, M.S.W., Bazin, N., and Sermon, P.A.: Chemical modification of silica gels. J. Sol–Gel Sci. Technol. 8, 499 (1997).CrossRefGoogle Scholar
Alothman, Z.: A Review: Fundamental aspects of silicate mesoporous materials. Materials (Basel) 5, 2874 (2012).CrossRefGoogle Scholar
Saito, S.T., Silva, G., Pungartnik, C., and Brendel, M.: Study of DNA-emodin interaction by FTIR and UV-vis spectroscopy. J. Photochem. Photobiol., B 111, 59 (2012).CrossRefGoogle ScholarPubMed
Darvishi, B., Farahmand, L., and Majidzadeh-A, K.: Stimuli-responsive mesoporous silica NPs as non-viral dual siRNA/chemotherapy carriers for triple negative breast cancer. Mol. Ther.-Nucleic Acids 7, 164 (2017).CrossRefGoogle ScholarPubMed
Meissner, J., Prause, A., Bharti, B., and Findenegg, G.H.: Characterization of protein adsorption onto silica nanoparticles: Influence of pH and ionic strength. Colloid Polym. Sci. 293, 3381 (2015).CrossRefGoogle ScholarPubMed
Lazaro, A., Vilanova, N., Barreto Torres, L.D., Resoort, G., Voets, I.K., and Brouwers, H.J.H.: Synthesis, polymerization, and assembly of nanosilica particles below the isoelectric point. Langmuir 33, 14618 (2017).CrossRefGoogle ScholarPubMed
Erickson, H.P.: Size and shape of protein molecules at the nanometer level determined by sedimentation, gel filtration, and electron microscopy. Biol. Proced. Online 11, 32 (2009).CrossRefGoogle ScholarPubMed
Fuertes, A.B., Valle-Vigón, P., and Sevilla, M.: Synthesis of colloidal silica nanoparticles of a tunable mesopore size and their application to the adsorption of biomolecules. J. Colloid Interface Sci. 349, 173 (2010).CrossRefGoogle ScholarPubMed
Conover, C.D., Linberg, R., Shum, K.L., and L Shorr, R.G.: The ability of polyethylene glycol conjugated bovine hemoglobin (PEG-Hb) to adequately deliver oxygen in both exchange transfusion and top-loaded rat models. Artif. Cells, Blood Substitutes, Biotechnol. 27, 93 (1999).CrossRefGoogle ScholarPubMed
Svergun, D.I., Ekströ, F., Vandegriff, K.D., Malavalli, A., Baker, D.A., Nilsson, C., and Winslow, R.M.: Solution structure of poly(ethylene) glycol-conjugated hemoglobin revealed by small-angle X-ray scattering: Implications for a new oxygen therapeutic. Biophys. J. 94, 173 (2008).CrossRefGoogle ScholarPubMed
Lipfert, J., Doniach, S., Das, R., and Herschlag, D.: Understanding nucleic acid–ion interactions. Annu. Rev. Biochem. 83, 813 (2014).CrossRefGoogle ScholarPubMed
Hydrophobicity, Polarity and Charge of Hemoglobin (2018): Available at: http://bioinformatics.org/jmol-tutorials/jtat/hemoglobin/5phob/chapter.htm (accessed September 20, 2019).Google Scholar
He, Q., Zhang, Z., Gao, F., Li, Y., and Shi, J.: In vivo biodistribution and urinary excretion of mesoporous silica nanoparticles: Effects of particle size and PEGylation. Small 7, 271 (2011).CrossRefGoogle ScholarPubMed
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