Abstract
Silica particles synthesized by precipitation method were in situ capped with Ethylenediaminetetraacetic acid (EDTA) and Hexamethylenetetramine (HMTA) compounds aiming to increase their biocompatibility. XRD, FTIR, TG/DSC, DLS and SEM analyses were performed to determine the crystalline structure, attached functional groups, thermal behaviour, size and morphology of silica particles. XRD analysis showed the amorphous structure of synthesized particles. FTIR results confirmed the formation of SiO2 particles and pointed about the functional groups (−CN, −CO,−OH etc.) attached on surface. Thermal analysis results showed that weight loss was due to removal of water and gradual degradation of EDTA molecules with rise of temperature, i.e. above 220 °C. The dynamic laser scattering measurements (zeta potential) depicted the strongest electrophoretic stability (− 30 mV) of EDTA-capped silica than virgin (− 13 mV) and particles capped with HMTA(− 24 mV). The SEM results revealed that virgin and silica particles capped with EDTA ligand exhibited spherical morphology with an average particle size of 210 nm and 280 nm, respectively. Whereas, HMTA-capped silica partilces showed hexagonal morphology with an average particle size of 240 nm. The in vitro cytotoxicity analysis was also carried out using human HepG2w, ATCC® HB-8065™ cell culture of 100 µg/ml concentration in Dulbecco’s Modified Eagle Medium (DMEM) solution maintained at 37 °C in the presence of CO2 environment. The results revealed that silica particles capped with EDTA (0.07 g) have shown remarkable biocompatibility (~ 96%) than virgin silica (~ 69%) due to bearing better hydrophobic characteristics. However, HMTA decomposed during synthesis which induced toxicity and agglomeration among silica particles. As a result, poor biocompatibility (~ 65%) was observed.
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References
Aewamatawong THK, Himada AKS, Kajima MINAO et al (2015) Acute and subacute pulmonary toxicity of low dose of ultrafine colloidal silica particles in mice after intratracheal instillation. Toxicol Pathol 24:958–965. https://doi.org/10.1080/01926230601094552
Alexis F, Pridgen E, Molnar LK, Farokhzad OC (2008) Reviews factors affecting the clearance and biodistribution of polymeric nanoparticles. Mol Pharm 5:505–515
AL-Othman ZA, Ali R, Naushad M (2012) Hexavalent chromium removal from aqueous medium by activated carbon prepared from peanut shell: adsorption kinetics, equilibrium and thermodynamic studies. Chem Eng J 184:238–247. https://doi.org/10.1016/j.cej.2012.01.048
Alshehri SM, Naushad M, Ahamad T et al (2014) Synthesis, characterization of curcumin based ecofriendly antimicrobial bio-adsorbent for the removal of phenol from aqueous medium. Chem Eng J 254:181–189. https://doi.org/10.1016/j.cej.2014.05.100
Anand KV, Chinnu MK, Kumar RM et al (2010) Thermal stability and optical properties of HMTA capped zinc sulfide nanoparticles. J Alloys Compd 496:665–668. https://doi.org/10.1016/j.jallcom.2010.02.159
Anand KV, Mohan R, Kumar RM et al (2012) Low-temperature synthesis of hexamethylenetetramine-stabilised ZnS nanoparticles and its photocatalytic properties. J Exp Nanosci 9:261–271. https://doi.org/10.1080/17458080.2012.656708
Arbenz A, Avérous L (2015) Chemical modi fi cation of tannins to elaborate aromatic biobased macromolecular architectures. Green Chem 17:2626–2646. https://doi.org/10.1039/c5gc00282f
Arooj S, Nazir S, Nadhman A et al (2015) Novel ZnO: ag nanocomposites induce significant oxidative stress in human fibroblast malignant melanoma (Ht144) cells. Beilstein J Nanotechnol 6:570–582. https://doi.org/10.3762/bjnano.6.59
Bushra R, Naushad M, Sharma G et al (2017) Synthesis of polyaniline based composite material and its analytical applications for the removal of highly toxic Hg2 + metal ion: antibacterial activity against E. coli. Korean J Chem Eng 34:1970–1979. https://doi.org/10.1007/s11814-017-0076-3
Chaúque EFC, Adelodun AA, Dlamini LN et al (2017) Synthesis and photocatalytic application of TiO2 nanoparticles immobilized on polyacrylonitrile nanofibers using EDTA chelating agents. Mater Chem Phys 192:108–124. https://doi.org/10.1016/j.matchemphys.2017.01.016
Chen C, Wu H, Huang H et al (2016) Synthesis of high valence silver-loaded mesoporous silica with strong antibacterial properties. Int J Environ Res Public Heal. https://doi.org/10.3390/ijerph13010099
Cho W, Choi M, Han BS et al (2007) Inflammatory mediators induced by intratracheal instillation of ultrafine amorphous silica particles. Toxicol Lett 175:24–33. https://doi.org/10.1016/j.toxlet.2007.09.008
Coasne B, Galarneau A, Di Renzo F et al (2006) Gas adsorption in mesoporous micelle-templated silicas: MCM-41, MCM-48, and SBA-15. Langmuir 22:11097–11105
Eom H, Choi J (2009) Toxicology in Vitro Oxidative stress of silica nanoparticles in human bronchial epithelial cell, Beas-2B. Toxicol Vitr 23:1326–1332. https://doi.org/10.1016/j.tiv.2009.07.010
Eyssa HM, Abulyazied DE, Abdulrahman M, Youssef HA (2017) Mechanical and physical properties of nanosilica/nitrile butadiene rubber composites cured by gamma irradiation. Egypt J Pet. https://doi.org/10.1016/j.ejpe.2017.06.004
Fan W, Shen B, Bu W et al (2014) A smart upconversion-based mesoporous silica nanotheranostic system for synergetic chemo-/radio-/photodynamic therapy and simultaneous MR/UCL imaging. Biomaterials 35:8992–9002. https://doi.org/10.1016/j.biomaterials.2014.07.024
Farooq A, Shukur A, Astley C et al (2018) Titania coating of mesoporous silica nanoparticles for improved biocompatibility and drug release within blood vessels. Acta Biomater. https://doi.org/10.1016/j.actbio.2018.06.024
Feng Y, Panwar N, Tng DJH et al (2016) The application of mesoporous silica nanoparticle family in cancer theranostics. Coord Chem Rev 319:86–109. https://doi.org/10.1016/j.ccr.2016.04.019
Ferrero ME (2016) Rationale for the successful management of EDTA chelation therapy in human burden by toxic metals. Biomed Res Int 2016:13. https://doi.org/10.1155/2016/8274504
Gazzano E, Ghiazza M, Polimeni M et al (2012) Physicochemical determinants in the cellular responses to nanostructured amorphous silicas. Toxicol Sci 128:158–170. https://doi.org/10.1093/toxsci/kfs128
Gedda G, Pandey S, Khan MS et al (2016) Synthesis of mesoporous titanium oxide for release control and high efficiency drug delivery of vinorelbine bitartrate. RSC Adv 6:13145–13151. https://doi.org/10.1039/c5ra14841c
Hao N, Li L, Tang F (2014) Shape-mediated biological effects of mesoporous silica nanoparticles. J Biomed Nanotechnol 10:2508–2538. https://doi.org/10.1166/jbn.2014.1940
Katwal R, Kaur H, Sharma G et al (2015) Electrochemical synthesized copper oxide nanoparticles for enhanced photocatalytic and antimicrobial activity. J Ind Eng Chem 31:173–184. https://doi.org/10.1016/j.jiec.2015.06.021
Kim S, Sung SH, Lim S, Ahn KH (2018) Com particle dispersion in silica-poly(vinyl alcohol) coatings: role of particle-polymer interaction. BioResources 13:3195–3207
Kobayashi Y, Morimoto H, Nakagawa T et al (2013) Preparation of Gd complex-immobilized silica particles and their application to MRI. ISRN Nanotechnol 2013:1–6
Kumar GA, Naik HSB, Viswanath R et al (2017) ScienceDirect Investigation on the structural and optical properties of hexamethylene tetramine (HMTA) capped ZnS: MN nanocrystals synthesized by microwave irradiation method. Mater Today Proc 4:3932–3941. https://doi.org/10.1016/j.matpr.2017.02.293
Lee B, Bhuta T, Craig J, Simpson J (2007) Methenamine hippurate for preventing urinary tract infections. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD003265.pub3
Li B, Zou X, Zhao Y et al (2013) Biofunctionalization of silica microspheres for protein separation. Mater Sci Eng, C 33:2595–2600. https://doi.org/10.1016/j.msec.2013.02.030
Li Z, Yu B, Cong H et al (2016) EDTA-modified DR/SiO2 adsorbent: preparation, characterization, and application in heavy metal adsorption. Integr Ferroelectr 169:1–6. https://doi.org/10.1080/10584587.2016.1162127
Liberman A, Martinez HP, Ta CN et al (2012) Hollow silica and silica-boron nano/microparticles for contrast-enhanced ultrasound to detect small tumors. Biomaterials 33:5124–5129. https://doi.org/10.1016/j.biomaterials.2012.03.066
Liberman A, Wu Z, Barback CV et al (2014) Hollow iron-silica nanoshells for enhanced high intensity focused ultrasound. J Surg Res 190:391–398. https://doi.org/10.1016/j.jss.2014.05.009
Lillo CR, Romero JJ, Portolés ML et al (2015) Organic coating of 1–2-nm-size silicon nanoparticles: effect on particle properties. Nano Res. https://doi.org/10.1007/s12274-015-0716-z
Lin W, Huang Y, Zhou X, Ma Y (2006) In vitro toxicity of silica nanoparticles in human lung cancer cells. Toxicol Appl Pharmacol 217:252–259. https://doi.org/10.1016/j.taap.2006.10.004
Linlin LI, Yanqi Z, Nanjing HAO et al (2012) Fabrication of PLGA coated silica nanorattle for controlling the drug release behavior. Mater Sci 57:3631–3638. https://doi.org/10.1007/s11434-012-5246-4
Mao H, Zhu K, Liu X et al (2016) Facile synthetic route to Fe3O4/silica nanocomposites pillared clay through cationic surfactant-aliphatic acid mixed system and application for magnetically controlled drug release. Microporous Mesoporous Mater 225:216–223. https://doi.org/10.1016/j.micromeso.2015.11.045
Milgroom A, Intrator M, Madhavan K et al (2014) Mesoporous silica nanoparticles as a breast-cancer targeting ultrasound contrast agent. Colloids Surf B Biointerfaces 116:652–657. https://doi.org/10.1016/j.colsurfb.2013.10.038
Nandanwar R, Singh P, Haque FZ (2015) Synthesis and characterization of SiO2 nanoparticles by sol-gel process and its degradation of methylene blue. Am Chem Sci J 5:1–10. https://doi.org/10.9734/ACSj/2014/10875
Napierska D, Thomassen LCJ, Lison D et al (2010) The nanosilica hazard: another variable entity. Part Fibre Toxicol 7:1–32
Naushad M, Ahamad T, Sharma G et al (2016) Synthesis and characterization of a new starch/SnO2 nanocomposite for efficient adsorption of toxic Hg2 + metal ion. Chem Eng J 300:306–316. https://doi.org/10.1016/j.cej.2016.04.084
Oviedo C, Rodríguez J (2003) EDTA: the chelating agent under environmental scrutiny. Quim Nova 26:901–905
Paciornik S, Mauricio MHP (2006) Evaluation of the effect of EDTA, EDTAC and citric acid on the microhardness of root dentine. Int Endod J 39:401–407. https://doi.org/10.1111/j.1365-2591.2006.01094.x
Panas A, Marquardt C, Nalcaci O et al (2012) Screening of different metal oxide nanoparticles reveals selective toxicity and inflammatory potential of silica nanoparticles in lung epithelial cells and macrophages. Nanotoxicology 49:1–15. https://doi.org/10.3109/17435390.2011.652206
Park E, Park K (2009) Oxidative stress and pro-inflammatory responses induced by silica nanoparticles in vivo and in vitro. Toxicol Lett 184:18–25. https://doi.org/10.1016/j.toxlet.2008.10.012
Polezhaeva OS, Yaroshinskaya NV, Ivanov VK (2008) Formation mechanism of nanocrystalline ceria in aqueous solutions of cerium (III) nitrate and hexamethylenetetramine. Inorg Mater 44:57–63. https://doi.org/10.1134/S0020168508010081
Pollard KM (2016) Silica, silicosis, and autoimmunity. Front Immunol 7:1–7. https://doi.org/10.3389/fimmu.2016.00097
Rahman IA, Padavettan V (2012) Synthesis of silica nanoparticles by sol-gel: size-dependent properties, surface modification, and applications in silica-polymer nanocomposites a review. J Nanomater. https://doi.org/10.1155/2012/132424
Rajput AB, Hazra S, Ghosh NN (2013) Synthesis and characterisation of pure single-phase CoFe2O4 nanopowder via a simple aqueous solution-based EDTA-precursor route. J Exp Nanosci 8:629–639. https://doi.org/10.1080/17458080.2011.582170
Rida MA, Harb F (2014) Synthesis and characterization of amorphous silica nanoparitcles from aqueous silicates uisng cationic surfactants. J Met Mater Miner 24:37–42
Sahoo B, Devi KSP, Dutta S et al (2014) Journal of colloid and interface science biocompatible mesoporous silica-coated superparamagnetic manganese ferrite nanoparticles for targeted drug delivery and MR imaging applications. J Colloid Interface Sci 431:31–41. https://doi.org/10.1016/j.jcis.2014.06.003
Saranya A, Devasena T, Sivaram H, Jayavel R (2019) Role of hexamine in ZnO morphologies at different growth temperature with potential application in dye sensitized solar cell. Mater Sci Semicond Process 92:108–115. https://doi.org/10.1016/j.mssp.2018.03.028
Sharma G, Pathania D, Naushad M, Kothiyal NC (2014) Fabrication, characterization and antimicrobial activity of polyaniline Th(IV) tungstomolybdophosphate nanocomposite material: efficient removal of toxic metal ions from water. Chem Eng J 251:413–421. https://doi.org/10.1016/j.cej.2014.04.074
Sharma RK, Sharma S, Dutta S (2015) Silica-nanosphere-based organic–inorganic hybrid nanomaterials: synthesis, functionalization and applications in catalysis. Green Chem 17:3207–3230. https://doi.org/10.1039/c5gc00381d
Sharma G, Kumar A, Naushad M et al (2016) Polyacrylamide@Zr(IV) vanadophosphate nanocomposite: ion exchange properties, antibacterial activity, and photocatalytic behavior. J Ind Eng Chem 33:201–208. https://doi.org/10.1016/j.jiec.2015.10.011
Song Y, Huang Z, Song Y, Tian Q, Liu X, She Z, Jiao J, Lu E, Deng Y (2014) The application of EDTA in drug delivery systems: doxorubicin liposomes loaded via NH 4 EDTA gradient. Int J Nanomed 9:3611–3621
Swift LP, Cutts SM, Rephaeli A et al (2003) Activation of adriamycin by the ph-dependent formaldehyde- releasing prodrug hexamethylenetetramine 1. Mol Cancer Ther 2:189–198
Tang F, Li L, Chen D (2012) Mesoporous silica nanoparticles: synthesis, biocompatibility and drug delivery. Adv Mater 24:1504–1534. https://doi.org/10.1002/adma.201104763
Thakur M, Sharma G, Ahamad T et al (2017) Efficient photocatalytic degradation of toxic dyes from aqueous environment using gelatin-Zr (IV) phosphate nanocomposite and its antimicrobial activity. Colloids Surf B Biointerfaces 157:456–463. https://doi.org/10.1016/j.colsurfb.2017.06.018
Venkateswaran S, Yuvakkumar R, Rajendran V (2013) Nano silicon from nano silica using natural resource (RHA) for solar cell fabrication. Phosphorus Sulfur Silicon Relat Elem 188:37–41. https://doi.org/10.1080/10426507.2012.740106
Waqas H, Salman MS, Riaz A et al (2015) Unique morphologies of zinc oxide synthesized by thermal decomposition and co-precipitation routes: ultraviolet absorption and luminescence characteristics. Cryst Res Technol 50:379–388. https://doi.org/10.1002/crat.201400484
Xu H, Yan F, Monson EE, Kopelman R (2003) Room-temperature preparation and characterization of poly (ethylene glycol) -coated silica nanoparticles for biomedical applications. J Biomed Mater Res Part A 66A:870–879
Zhang Q, Ge J, Goebl J et al (2009) Rattle-type silica colloidal particles prepared by a surface-protected etching process. Nano Res 2:583–591. https://doi.org/10.1007/s12274-009-9060-5
Zhao B, Ryan KM, O’Reilly E, McCarthy C (2017) Temperature controlled shape evolution of iron oxide nanostructures in HMTA media. RSC Adv 7:26328–26334. https://doi.org/10.1039/c7ra03603e
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Authors would like to recognize PINSTECH, IBGE and PIEAS University for providing synthesis and characterization facilities to complete this work.
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According to author’s knowledge, EDTA (0.07g)-capped silica particles synthesized by precipitation method, showing excellent cell viability (~96%) for Human hepatocellular carcinoma cell line (HepG2, ATCC® HB-8065™) is first time reported. The EDTA-capped silica particles have greater potential for their utilization in biomedical industry.
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Waqas, H., Khan, T.A., Hameed, A. et al. In vitro cytotoxicity study of virgin, ethylenediaminetetraacetic acid- and hexamethylenetetramine-capped silica particles synthesized by precipitation method. Chem. Pap. 74, 1779–1789 (2020). https://doi.org/10.1007/s11696-019-01021-3
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DOI: https://doi.org/10.1007/s11696-019-01021-3