{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T11:50:26Z","timestamp":1768477826954,"version":"3.49.0"},"reference-count":152,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2018,8,13]],"date-time":"2018-08-13T00:00:00Z","timestamp":1534118400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Silica is one of the most abundant minerals in the Earth\u2019s crust, and over time it has been introduced first into human life and later into engineering. Silica is present in the food chain and in the human body. As a biomaterial, silica is widely used in dentistry, orthopedics, and dermatology. Recently amorphous sol-gel SiO2 nanoparticles (NPs) have appeared as nanocarriers in a wide range of medical applications, namely in drug\/gene target delivery and imaging diagnosis, where they stand out for their high biocompatibility, hydrophilicity, enormous flexibility for surface modification with a high payload capacity, and prolonged blood circulation time. The sol-gel process is an extremely versatile bottom-up methodology used in the synthesis of silica NPs, offering a great variety of chemical possibilities, such as high homogeneity and purity, along with full scale pH processing. By introducing organic functional groups or surfactants during the sol-gel process, ORMOSIL NPs or mesoporous NPs are produced. Colloidal route, biomimetic synthesis, solution route and template synthesis (the main sol-gel methods to produce monosized silica nanoparticles) are compared and discussed. This short review goes over some of the emerging approaches in the field of non-porous sol-gel silica NPs aiming at medical applications, centered on the syntheses processes used.<\/jats:p>","DOI":"10.3390\/molecules23082021","type":"journal-article","created":{"date-parts":[[2018,8,13]],"date-time":"2018-08-13T11:27:13Z","timestamp":1534159633000},"page":"2021","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":146,"title":["Sol-Gel Silica Nanoparticles in Medicine: A Natural Choice. Design, Synthesis and Products"],"prefix":"10.3390","volume":"23","author":[{"given":"M. Clara","family":"Gon\u00e7alves","sequence":"first","affiliation":[{"name":"Departamento de Engenharia Qu\u00edmica, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal"},{"name":"CQE, Centro de Qu\u00edmica Estrutural, Instituto Superior T\u00e9cnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2018,8,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Gon\u00e7alves, M.C., and Margarido, F. (2015). Materials for Construction and Civil Engineering: Science, Processing, and Design, Springer.","DOI":"10.1007\/978-3-319-08236-3"},{"key":"ref_2","unstructured":"(2018, May 01). IMA Europe. Available online: https:\/\/www.ima-europe.eu\/about-industrial-minerals\/industrial-minerals-ima-europe\/silica."},{"key":"ref_3","unstructured":"(2018, May 01). ASAP Association of Synthetic Amorphous Silica. Available online: http:\/\/www.asasp.eu\/index.php\/about-asasp\/activities."},{"key":"ref_4","unstructured":"(2018, May 01). nepSI\u2014The European Network on Silica. Available online: https:\/\/ec.europa.eu\/growth\/tools-databases\/eip-raw-materials\/en\/content\/nepsi-european-network-silica."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ha, S.-W., Weitzmann, M.N., and Beck, G.R. (2013). Dental and Skeletal Applications of Silica-Based. Nanobiomaterials in Clinical Dentistry, Elsevier.","DOI":"10.1016\/B978-1-4557-3127-5.00004-0"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1007\/978-3-540-88552-8_16","article-title":"The application of silicon and silicates in dentistry: A review","volume":"Volume 47","author":"Luhrs","year":"2009","journal-title":"Biosilica in Evolution, Morphogenesis, and Nanobiotechnology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2090","DOI":"10.1002\/jbm.a.36061","article-title":"Silicates in orthopedics and bone tissue engineering materials","volume":"105","author":"Zhou","year":"2017","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5456","DOI":"10.1021\/am405013t","article-title":"Mesoporous Silica Nanoparticles\/Hydroxyapatite Composite Coated Implants to Locally Inhibit Osteoclastic Activity","volume":"6","author":"Zhu","year":"2014","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_9","unstructured":"(2018, May 01). AAA American Academy of Dermatology. Available online: https:\/\/www.aad.org\/media\/news-releases\/--small-changes-in-skin-care-routine-can-significantly-improve-skin-affected-by-acne-and rosacea."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Navarro, M., and Serra, T. (2016). Biomimetic mineralization of ceramics and glasses. Biominer. Biomater. Fundam. Appl., 315\u2013338.","DOI":"10.1016\/B978-1-78242-338-6.00011-9"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Brunner, T.J., Stark, W.J., and Boccaccini, A.R. (2010). Nanoscale Bioactive Silicate Glasses in Biomedical Applications. Nanoscale.","DOI":"10.1002\/9783527610419.ntls0142"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Chen, J., Fang, L., Zhang, Y., Zhu, H., and Cao, S. (2014). Silica-Based Scaffolds: Fabrication, Synthesis and Properties in: Frontiers in Biomaterials. The Design, Synthetic Strategies and Biocompatibility of Polymer Scaffolds for Biomedical Application, Bentham Science.","DOI":"10.2174\/9781608058761114010014"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.matlet.2013.05.088","article-title":"A biological scaffold filled with silica and simultaneously crosslinked with polyurethane","volume":"106","author":"Castellano","year":"2013","journal-title":"Mater. Lett."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1021\/cr300213b","article-title":"Nanomaterials for Theranostics: Recent Advances and Future Challenges","volume":"115","author":"Lim","year":"2015","journal-title":"Chem. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Matos, J.C., Gon\u00e7alves, M.C., and Monteiro, G.A. (2015). Silica and ORMOSIL nanoparticles for gene delivery. Nano Based Drug Delivery, IAPC Open Book Platform.","DOI":"10.5599\/obp.8.9"},{"key":"ref_16","unstructured":"Ali, N., and Seifalian, A. (2014). Multifunctional core-shell nanostructures. Nanomedicine, One Central Press Office."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Bharti, C., Nagaich, U., Pal, A.K., and Gulati, N. (2015). Mesoporous silica nanoparticles in target drug delivery: A Review. Int. J. Pharm. Invest., 5.","DOI":"10.4103\/2230-973X.160844"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.nano.2015.10.018","article-title":"Advances in Silica based nanoparticles for target cancer therapy","volume":"12","author":"Yang","year":"2016","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1021\/cm402592t","article-title":"Multifunctional Mesoporous Silica nanoparticles as a Universal Platform for Drug Delivery","volume":"26","author":"Argyo","year":"2014","journal-title":"Chem. Mater."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"12320","DOI":"10.1002\/anie.201403036","article-title":"Engineered Nanoparticles for Drug Delivery in Cancer Therapy","volume":"53","author":"Sun","year":"2014","journal-title":"Angew. Rev. Int. Ed."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.nantod.2013.04.007","article-title":"Nonporous silica nanoparticles for nanomedicine application","volume":"8","author":"Tang","year":"2013","journal-title":"Nano Today"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Korzeniowska, B., Nooney, R., Wencel, D., and McDonagh, C. (2013). Silica Nanoparticles for cell imaging and intracellular sensing. Nanotechnology, 24.","DOI":"10.1088\/0957-4484\/24\/44\/442002"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Vallet-Reg\u00ed, M. (2012). Mesoporous Silica nanoparticles: Their projection in Nanomedicine. ISRN Mater. Sci.","DOI":"10.5402\/2012\/608548"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2874","DOI":"10.3390\/ma5122874","article-title":"A Review: Fundamental Aspects of Silicate Mesoporous Materials","volume":"5","author":"ALOthman","year":"2012","journal-title":"Materials"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1007\/s11948-015-9705-6","article-title":"Defining Nano, Nanotechnology and Nanomedicine: Why Should It Matter?","volume":"5","author":"Satalkar","year":"2016","journal-title":"Sci. Eng. Ethics"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.molonc.2008.04.001","article-title":"Imaging and cancer: A review","volume":"2","author":"Fass","year":"2008","journal-title":"Mol. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1016\/S1734-1140(12)70901-5","article-title":"Nanoparticles as drug delivery systems","volume":"64","author":"Wilczewska","year":"2012","journal-title":"Pharmacol. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Watermann, A., and Brieger, J. (2017). Mesoporous Silica Nanoparticles as Drug Delivery Vehicles in Cancer. Nanomaterials, 7.","DOI":"10.3390\/nano7070189"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Vallet-Regi, M., Colilla, M., Izquierdo-Barba, I., and Manzano, M. (2018). Mesoporous Silica Nanoparticles for Drug Delivery: Current Insights. Molecules, 23.","DOI":"10.3390\/molecules23010047"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.apsb.2018.01.007","article-title":"Mesoporous silica nanoparticles for drug and gene delivery","volume":"8","author":"Zhou","year":"2018","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.1038\/mt.2011.105","article-title":"Mesoporous Silica Nanoparticles as Drug Delivery Systems for Targeted Inhibition of Notch Signaling in Cancer","volume":"19","author":"Mamaeva","year":"2011","journal-title":"Mol. Ther."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Wen, J., Yang, K., Liu, F., Li, H., Xu, Y., and Sun, S. (2017). Diverse gatekeepers for mesoporous silica nanoparticle based drug delivery systems. Chem. Soc. Rev., 19.","DOI":"10.1039\/C7CS00219J"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.addr.2013.11.009","article-title":"Cancer nanotechnology: The impact of passive and active targeting in the era of modern cancer biology","volume":"66","author":"Bertrand","year":"2014","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.7150\/thno.14858","article-title":"The Smart Drug Delivery System and Its Clinical Potential","volume":"6","author":"Liu","year":"2016","journal-title":"Theranostics"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"8778","DOI":"10.1021\/ja200328s","article-title":"pH-Triggered Controlled Drug Release from Mesoporous Silica Nanoparticles via Intracelluar Dissolution of ZnO Nanolids","volume":"133","author":"Muhammad","year":"2011","journal-title":"J. Am. Chem. Soc."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5257","DOI":"10.2147\/IJN.S112030","article-title":"Amorphous silica nanoparticles trigger vascular endothelial cell injury through apoptosis and autophagy via reactive oxygen species-mediated MAPK\/Bcl-2 and PI3K\/Akt\/mTOR signaling","volume":"11","author":"Guo","year":"2016","journal-title":"Int. J. Nanomed."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Han, W., Chilkoti, A., and L\u00f3pez, G. (2017). Self-assembled hybrid elastin-like polypeptide\/silica nanoparticles enable triggered drug release. Nanoscale, 18.","DOI":"10.1039\/C7NR00172J"},{"key":"ref_38","unstructured":"Iler, R.K. (1978). The Chemistry of Silica: Solubility, Polymerization, Colloid and Surface Properties, and Biochemistry, John Wiley."},{"key":"ref_39","unstructured":"Brinker, C.J., and Scherer, G.W. (1990). Sol-Gel Science. The Physics and Chemistry of Sol-Gel Processing, Academic Press."},{"key":"ref_40","unstructured":"(2018, May 01). FDA US Food & Drug Administration CFR\u2014Code of Federal Regulations Title 21, Available online: https:\/\/www.accessdata.fda.gov\/scripts\/cdrh\/cfdocs\/cfcfr\/CFRSearch.cfm?fr=182.1711&SearchTerm=silica."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Kasaai, M.R. (2015). Nanosized Particles of Silica and Its Derivatives for Applications in Various Branches of Food and Nutrition Sectors. J. Nanotechnol.","DOI":"10.1155\/2015\/852394"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Go, M.-R., Bae, S.-H., Kim, H.-J., Yu, J., and Choi, S.-J. (2017). Interactions between Food Additive Silica Nanoparticles and Food Matrices. Front. Microbiol., 8.","DOI":"10.3389\/fmicb.2017.01013"},{"key":"ref_43","unstructured":"(2018, May 01). The Sol Gel Gateway. Available online: https:\/\/www.solgel.com."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1021\/nl0482478","article-title":"Bright and Stable Core\u2212Shell Fluorescent Silica Nanoparticles","volume":"5","author":"Ow","year":"2005","journal-title":"Nano Lett."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1021\/nl803405h","article-title":"Fluorescent Silica Nanoparticles with Efficient Urinary Excretion for Nanomedicine","volume":"9","author":"Burns","year":"2009","journal-title":"Nano Lett."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1038\/nnano.2016.164","article-title":"Ultrasmall nanoparticles induce ferroptosis in nutrient-deprived cancer cells and suppress tumour growth","volume":"11","author":"Kim","year":"2016","journal-title":"Nat. Nanotechnol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Burns, A., Ow, H., and Wiesner, U. (2016). Fluorescent core\u2013shell silica nanoparticles: towards \u201cLab on a Particle\u201d architectures for nanobiotechnology. Chem. Soc. Rev., 1028\u20131042.","DOI":"10.1039\/B600562B"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.mattod.2015.08.022","article-title":"Magnetite nanoparticles for cancer diagnosis, treatment, and treatment monitoring: recent advances","volume":"19","author":"Revia","year":"2016","journal-title":"Mater. Today"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Foglia, M.L., Alvarez, G.S., Catalano, P.N., Mebert, A.M., Diaz, L.E., Coradin, T., and Desimone, M.F. (2011). Recent Patents on the Synthesis and Application of Silica Nanoparticles for Drug Delivery. Recent Pat. Biotechnol., 5.","DOI":"10.2174\/187220811795655887"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"M\u00fcller, W.E.G., and Grachev, M.A. (2009). Biosilica in Evolution, Morphogenesis, and Nano-biotechnology, Springer.","DOI":"10.1007\/978-3-540-88552-8"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.earscirev.2018.01.018","article-title":"The Messinian diatomite deposition in the Mediterranean region and its relationships to the global silica cycle","volume":"178","author":"Pellegrino","year":"2018","journal-title":"Earth Sci. Rev."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1002\/jpln.200521981","article-title":"Silicon pools and fluxes in soils and landscapes\u2014A review","volume":"169","author":"Sommer","year":"2006","journal-title":"J. Plant Nutr. Soil Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1073\/pnas.91.1.11","article-title":"The anomaly of silicon in plant biology","volume":"91","author":"Epstein","year":"1994","journal-title":"Proc. Nat. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S0065-2113(08)60734-8","article-title":"Silica in Soils, Plants, and Animals","volume":"19","author":"Jones","year":"1967","journal-title":"Adv. Agron."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1093\/aob\/mcm247","article-title":"Silica in Plants: Biological, Biochemical and Chemical Studies","volume":"100","author":"Currie","year":"2007","journal-title":"Ann. Bot."},{"key":"ref_56","first-page":"641","article-title":"Silicon. Annual Review of Plant. Physiology and Plant","volume":"50","author":"Epstein","year":"1999","journal-title":"Mol. Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s10658-010-9625-x","article-title":"Silicon-enhanced resistance to rice blast is attributed to silicon-mediated defense resistance and its role as physical barrier","volume":"128","author":"Sun","year":"2010","journal-title":"Eur. J. Plant. Pathol."},{"key":"ref_58","first-page":"94","article-title":"The chemistry of silica and its potential health benefits","volume":"11","author":"Martin","year":"2007","journal-title":"J. Nutr. Health Aging"},{"key":"ref_59","first-page":"99","article-title":"Silicon and bone health","volume":"11","author":"Jugdaohsingh","year":"2007","journal-title":"J. Nutr. Health Aging"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"423","DOI":"10.3233\/JAD-2012-121231","article-title":"Silicon-rich mineral water as a non-invasive test of the \u2018aluminum hypothesis\u2019 in Alzheimer\u2019s disease","volume":"33","author":"Davenward","year":"2013","journal-title":"J. Alzheimers Dis."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1093\/aje\/kwn348","article-title":"Aluminum and silica in drinking water and the risk of Alzheimer\u2019s disease or cognitive decline: findings from 15-year follow-up of the PAQUID cohort","volume":"169","author":"Rondeau","year":"2009","journal-title":"Am. J. Epidemiol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Schwarz, K. (1977). Silicon, fibre, and atherosclerosis. Lancet, 1.","DOI":"10.1016\/S0140-6736(77)91945-6"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Heinemann, S., Coradin, T., and Desimone, M.F. (2013). Bio-inspired silica\u2013collagen materials: applications and perspectives in the medical field. Biomater. Sci., 7.","DOI":"10.1039\/c3bm00014a"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1017\/S0007114509311757","article-title":"The comparative absorption of silicon from different foods and food supplements","volume":"102","author":"Sripanyakorn","year":"2009","journal-title":"Br. J. Nutr."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Jurki\u0107, L.M., Cepanec, I., Paveli\u0107, S.K., and Paveli\u0107, K. (2013). Biological and therapeutic effects of ortho-silicic acid and some ortho-silicic acid-releasing compounds: New perspectives for therapy. Nutr. Metab., 10.","DOI":"10.1186\/1743-7075-10-2"},{"key":"ref_66","unstructured":"(2018, May 01). Cancer-Causing Substances in the Environment: Crystalline Silica, Available online: https:\/\/www.cancer.gov\/about-cancer\/causes-prevention\/risk\/substances\/crystalline-silica."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Pollard, K.M. (2016). Silica, Silicosis, and Autoimmunity. Front. Immunol., 7.","DOI":"10.3389\/fimmu.2016.00097"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"15790","DOI":"10.1021\/ja304907c","article-title":"Processing Pathway Dependence of Amorphous Silica Nanoparticle Toxicity: Colloidal vs Pyrolytic","volume":"134","author":"Zhang","year":"2012","journal-title":"J. Am. Chem. Soc."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1016\/j.ijheh.2017.03.010","article-title":"15 years of monitoring occupational exposure to respirable dust and quartz within the European industrial minerals sector","volume":"220","author":"Zilaout","year":"2017","journal-title":"Int. J. Hyg. Environ. Health"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Petushkov, A., Ndiege, N., Salem, A.K., and Larsen, S.C. (2010). Toxicity of Silica Nanomaterials: Zeolites, Mesoporous Silica, and Amorphous Silica Nanoparticles. Advances in Molecular Toxicology, Elsevier.","DOI":"10.1016\/S1872-0854(10)04007-5"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2967","DOI":"10.1007\/s00204-017-1993-y","article-title":"Toxicology of silica nanoparticles: An update","volume":"91","author":"Murugadoss","year":"2017","journal-title":"Arch. Toxicol."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Yu, Y., Li, Y., Wang, W., Jin, M., Du, Z., Li, Y., Duan, J., Yu, Y., and Sun, Z. (2013). Acute Toxicity of Amorphous Silica Nanoparticles in Intravenously Exposed ICR Mice. PLoS ONE.","DOI":"10.1371\/journal.pone.0061346"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1021\/acsnano.6b07461","article-title":"Specifically Formed Corona on Silica Nanoparticles Enhances Transforming Growth Factor \u03b21 Activity in Triggering Lung Fibrosis","volume":"11","author":"Wang","year":"2017","journal-title":"ACS Nano"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1007\/s002040100266","article-title":"Health Hazards due to the inhalation of amorphous silica","volume":"75","author":"Merget","year":"2001","journal-title":"Arch. Toxicol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s11051-008-9417-9","article-title":"Toxicity of amorphous silica nanoparticles in mouse keratinocytes","volume":"11","author":"Yu","year":"2009","journal-title":"J. Nanopart. Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"6829","DOI":"10.1021\/nn301622h","article-title":"Skin Penetration and Cellular Uptake of Amorphous Silica Nanoparticles with Variable Size, Surface Functionalization, and Colloidal Stability","volume":"6","author":"Rancant","year":"2012","journal-title":"ACS Nano"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ajps.2016.07.006","article-title":"Application of quality by design in the current drug development","volume":"12","author":"Zhang","year":"2017","journal-title":"Asian J. Pharm. Sci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.ejps.2016.01.003","article-title":"Quality by Design case study 1: Design of 5-fluorouracil loaded lipid nanoparticles by the W\/O\/W double emulsion-solvent evaporation method","volume":"84","author":"Amasya","year":"2016","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Yu, L.X., Amidon, G., Khan, M.A., Hoag, S.W., Polli, J., Raju, G.K., and Woodcock, J. (2014). Understanding Pharmaceutical Quality by Design. AAPS J., 16.","DOI":"10.1208\/s12248-014-9598-3"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.ejps.2012.06.009","article-title":"Strategic funding priorities in the pharmaceutical sciences allied to Quality by Design (QbD) and Process Analytical Technology (PAT)","volume":"47","author":"Aksu","year":"2012","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/0167-5699(91)90009-I","article-title":"The role of complement in inflammation and phagocytosis","volume":"12","author":"Frank","year":"1991","journal-title":"Immunol. Today"},{"key":"ref_82","unstructured":"Ratner, B.D., Hoffman, A.S., Schoen, F.J., and Lemons, J.E. (2004). The complement system. Biomaterials Science: An Introduction to Materials in Medicine, Elsevier Academic Press."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1126\/science.8128245","article-title":"Biodegradable long circulating polymeric nanospheres","volume":"263","author":"Gref","year":"1994","journal-title":"Science"},{"key":"ref_84","unstructured":"Ratner, B.D., Hoffman, A.S., Schoen, F.J., and Lemons, J.E. (2004). Innate and adaptive immunity: The immune response to foreign materials. Biomaterials Science: An. Introduction to Materials in Medicine, Elsevier Academic Press."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.ijpharm.2005.10.010","article-title":"Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles","volume":"307","author":"Owens","year":"2006","journal-title":"Int. J. Pharm."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1016\/j.nano.2015.05.005","article-title":"Nanoparticles in medicine: Current challenges facing inorganic nanoparticle toxicity assessments and standardizations","volume":"11","author":"Grainger","year":"2015","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1021\/j150516a002","article-title":"The Solubility of Amorphous Silica in Water","volume":"58","author":"Alexander","year":"1954","journal-title":"J. Phys. Chem."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Croissant, J.G., Fatieiev, Y., and Khashab, N.M. (2017). Degardability and Clearance of silicon, Organosilica, Silsesquioxane, Silica Mixed Oxide, and Mesoporous Silica Nanoparticles. Adv. Mater., 29.","DOI":"10.1002\/adma.201604634"},{"key":"ref_89","unstructured":"(2018, May 01). Prevention\/Risk\/Substances\/Crystalline-Silica, Available online: https:\/\/www.cancer.gov\/about-cancer\/causes."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2545","DOI":"10.1039\/c2cs15327k","article-title":"Design of polymeric nanoparticles for biomedical delivery applications","volume":"41","author":"Elsabahy","year":"2012","journal-title":"Chem. Soc. Rev."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1038\/nbt1340","article-title":"Renal clearance of quantum dots","volume":"25","author":"Choi","year":"2007","journal-title":"Nat. Biotechnol."},{"key":"ref_92","unstructured":"Pascal, R. Sol-gel processes and products. Encyclopedia of Glass Science, Technology, History, and Culture, John Wiley and Sons. in press."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/978-3-642-55486-5_11","article-title":"Studies of biosilicas; structural aspects, chemical principles, model studies and the future","volume":"33","author":"Perry","year":"2003","journal-title":"Prog. Mol. Subcell. Biol."},{"key":"ref_94","first-page":"40","article-title":"Structural Aspects of biogenic silica","volume":"121","author":"Mann","year":"1986","journal-title":"Ciba Found. Symp."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1557\/jmr.2016.459","article-title":"Biosilica from diatoms microalgae: smart materials from bio-medicine to photonics","volume":"32","author":"Ragni","year":"2016","journal-title":"J. Mater. Res."},{"key":"ref_96","first-page":"228","article-title":"In vitro cytotoxicity and quantitative silica analysis of diatomaceous earth products","volume":"41","author":"Bye","year":"1984","journal-title":"Br. J. Ind. Med."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Zhang, H., Shahbazi, M., M\u01dfkil\u01df, E., da Silva, T., Reis, R., and Salonen, J. (2013). Diatom silica microparticles for sustained release and permeation enhancement following oral delivery of prednisone and mesalamine. Biomaterials, 3.","DOI":"10.1016\/j.biomaterials.2013.08.035"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2947","DOI":"10.1002\/adma.200803778","article-title":"Diatomaceous lessons in nanotechnology and advanced materials","volume":"21","author":"Losic","year":"2009","journal-title":"Adv. Mater."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.tibtech.2008.11.003","article-title":"The glass menagerie: diatoms for novel applications in nanotechnology","volume":"27","author":"Gordon","year":"2008","journal-title":"Trends Biotechnol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1021\/nl015581k","article-title":"Nanostructure of diatom silica surfaces and of biomimetic analogues","volume":"2","author":"Noll","year":"2002","journal-title":"Nano Lett."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.dib.2016.11.072","article-title":"A systematic databasing of diatoms from different geographical localities and sites of Haryana for advancing validation of forensic diatomology","volume":"10","author":"Saini","year":"2017","journal-title":"Data Brief"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.cis.2017.04.005","article-title":"Silica-based systems for oral delivery of drugs, macomolecules and cells","volume":"249","author":"Diab","year":"2017","journal-title":"Adv. Colloid Interface Sci."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1016\/j.colsurfb.2014.10.047","article-title":"Surface Engineering of silica nanoparticles for oral insulin delivery: Characterization and cell toxicity studies","volume":"123","author":"Andreani","year":"2014","journal-title":"Colloid. Surf. B"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.ejpb.2015.03.027","article-title":"Effect of mucoadhesive polymers on the in vitro performance of insulin-loaded silica nanoparticles: interactions with mucin and biomembrane models","volume":"93","author":"Andreani","year":"2015","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.ejps.2005.06.009","article-title":"Release evaluation of drugs from ordered three-dimensional silica structures","volume":"26","author":"Martinez","year":"2005","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1039\/b616746b","article-title":"Enhanced release of itraconazole from ordered mesoporous SBA-15 silica materials","volume":"13","author":"Mellaerts","year":"2007","journal-title":"Chem. Commun."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"8116","DOI":"10.1021\/ja062286z","article-title":"Confinement and Controlled Release of Bisphosphonates on Ordered Mesoporous Silica-Based Materials","volume":"128","author":"Balas","year":"2006","journal-title":"J. Am. Chem."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"P\u00e9rez-Esteve, E., Ruiz-Rico, M., Fuentes, A., Marcos, M., Sancenon, F., and Martinez-Manez, R. (2016). Enrichment of stirred yogurts with folic acid encapsulated in pH-responsive mesoporous silica particles: Bioaccessibility modulation and physico-chemical characterization. LWT Food Sci. Technol., 72.","DOI":"10.1016\/j.lwt.2016.04.061"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"2382","DOI":"10.1021\/ja0772086","article-title":"Enzyme-Responsive Snap-Top Covered Silica Nanocontainers","volume":"130","author":"Patel","year":"2008","journal-title":"J. Am. Chem. Soc."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Popat, A., Jambhrunkar, S., Zhang, J., Yang, J., Zhang, H., Meka, A., and Yu, C. (2014). Programmable drug release using bioresponsive mesoporous silica nanoparticles for site-specific oral drug delivery. Chem. Commun., 50.","DOI":"10.1039\/C4CC00620H"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.colsurfb.2015.12.040","article-title":"Core-shell microcapsules of solid lipid nanoparticles and mesoporous silica for enhanced oral delivery of curcumin","volume":"140","author":"Kim","year":"2016","journal-title":"Colloids Surf. B"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.2217\/nnm.11.29","article-title":"Silica microcapsules from diatoms as new carrier for delivery of therapeutics","volume":"6","author":"Aw","year":"2011","journal-title":"Nanomedicine"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"4728","DOI":"10.1021\/la0494019","article-title":"Amine-Terminated Dendrimers as Biomimetic Templates for Silica Nanosphere Formation","volume":"20","author":"Knecht","year":"2004","journal-title":"Langmuir"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.1021\/la011106q","article-title":"Interactions of Amino-Containing Peptides with Sodium Silicate and Colloidal Silica:\u2009 A Biomimetic Approach of Silicification","volume":"18","author":"Coradin","year":"2002","journal-title":"Langmuir"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"4890","DOI":"10.1021\/cm049058t","article-title":"Dendrimer-Mediated Formation of Multicomponent Nanospheres","volume":"16","author":"Knecht","year":"2004","journal-title":"Chem. Mater."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Bauer, C.A., Robinson, D.B., and Simmons, B.A. (2007). Silica particle formation in confined environments via bioinspired polyamine catalysis at near-neutral pH. Small, 3.","DOI":"10.1002\/smll.200600352"},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Jan, J.S., Lee, S.L., Carr, C.S., and Schantz, D.F. (2005). Biomimetic Synthesis of Inorganic Nanospheres. Chem. Mater., 17.","DOI":"10.1021\/cm0504440"},{"key":"ref_118","unstructured":"Jin, R.H., and Yuan, J.J. (2009). Learning from Biosilica: Nanostructured Silicas and Their Coatings on Substrates by Programmable Approaches. Adv. Biomim., 39."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Hartlen, K.D., Athanasopoulo, A.P.T., and Kitaev, V. (2008). Facile preparation of highly monodisperse small silica spheres (15 to > 200 nm) suitable for colloidal templating and formation of ordered arrays. Langmuir, 24.","DOI":"10.1021\/la7025285"},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Yokoi, T., Sakomoto, Y., Terasaki, O., Kubota, Y., Okubo, T., and Tatsumi, T. (2006). Periodic Arrangement of Silica Nanospheres Assisted by Amino Acids. J. Am. Chem Soc., 128.","DOI":"10.1021\/ja065071y"},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Davis, T.M., Snyder, M.A., Krohn, J.E., and Tsapatsis, M. (2006). Nanoparticles in Lysine\u2212Silica Sols. Chem. Mater., 18.","DOI":"10.1021\/cm061982v"},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Snyder, M.A., Lee, J.A., Davis, T.M., Scriven, L.E., and Tsapatsis, M. (2007). Silica nanoparticle crystals and ordered coatings using lys-sil and a novel coating device. Langmuir, 23.","DOI":"10.1021\/la701063v"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Yuan, J.J., Mykhaylyk, O.O., Ryan, A.J., and Armes, S.P. (2007). Cross-Linking of Cationic Block Copolymer Micelles by Silica Deposition. J. Am. Chem. Soc., 129.","DOI":"10.1021\/ja0674946"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.jcis.2009.05.074","article-title":"Biomimetic synthesis of copolymer-silica nanoparticles with tunable compositions and surface property","volume":"338","author":"Li","year":"2009","journal-title":"J. Colloid Interface Sci."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.jcis.2017.07.115","article-title":"Synthesis of silica nanoparticles using biomimetic mineralization with polyallylamine hydrochloride","volume":"507","author":"Kang","year":"2017","journal-title":"J. Colloid Interface Sci."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.tibtech.2008.06.009","article-title":"Bioinspired enzyme encapsulation for biocatalysis","volume":"26","author":"Betancor","year":"2008","journal-title":"Trends Biotechnol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1007\/s11705-014-1421-2","article-title":"Immobilizayion ofb-glucuronidase in lysozyme-induced biosilica particles to imporve its stability","volume":"8","author":"Song","year":"2014","journal-title":"Front. Chem. Sci. Eng."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1128\/AEM.06698-11","article-title":"Live diatom silica immobilization of multimeric and redox-active enzymes","volume":"78","author":"Sheppard","year":"2012","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1007\/s10529-012-0924-5","article-title":"Alkyl-substituted methoxylanes enhance the activity and stability of d-amino acid oxidase encapsulated in biomimetic silica","volume":"34","author":"Kuan","year":"2012","journal-title":"Biotechnol. Lett."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"2631","DOI":"10.1021\/bm060166d","article-title":"Application of microfluid reactor for screening cancer produg activation using silica-immmobilized nitrobenzene nitroreductase","volume":"7","author":"Berne","year":"2006","journal-title":"Biomacromolecules"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1080\/02648725.2010.10648146","article-title":"Co-immobilization coupled enzyme systems in biotechnology","volume":"27","author":"Betancor","year":"2010","journal-title":"Biotechnol. Genet. Eng. Rev."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"3687","DOI":"10.1021\/la504978r","article-title":"Protein-Templated Biomimetic Silica Nanoparticles","volume":"31","author":"Jackson","year":"2015","journal-title":"Langmuir"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"3122","DOI":"10.1039\/B306994J","article-title":"Synthesis of sub-200 nm silsesquioxane particles using a modified St\u00f6ber sol\u2013gel route","volume":"13","author":"Arkhreeva","year":"2003","journal-title":"J. Mater. Chem."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"4847","DOI":"10.1021\/ja01167a001","article-title":"Theory, Production and Mechanism of Formation of Monodispersed Hydrosols","volume":"72","author":"LaMer","year":"1950","journal-title":"J. Am. Chem. Soc."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.ijpharm.2014.10.068","article-title":"CapsMorph\u00ae technology for oral delivery-theory, prepatration and characterization","volume":"482","author":"Wei","year":"2015","journal-title":"Int. J. Pharm."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.carbpol.2016.08.015","article-title":"Silica Vectors for Smart Textiles","volume":"156","author":"Matos","year":"2017","journal-title":"Carbohydr. Polym."},{"key":"ref_137","unstructured":"Evonik (2018, May 01). Power to Create. Available online: http:\/\/www.aerosil.com\/product\/aerosil\/en\/industries\/pharmaceuticals\/aeroperl-300-pharma\/."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.jconrel.2008.10.014","article-title":"Silica-lipid hybrid (SLH) microcapsules: a novel oral delivery system for poorly soluble drugs","volume":"134","author":"Tan","year":"2009","journal-title":"J. Control. Release"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1021\/mp9002442","article-title":"Silica nanoparticles to control the lipase-mediated digestion of lipid-based oral delivery systems","volume":"7","author":"Tan","year":"2010","journal-title":"Mol. Pharm."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"2779","DOI":"10.1021\/la500094b","article-title":"The role of porous nanostructure in controlling the lipase-mediated digestion of lipid loaded into silica particles","volume":"30","author":"Joyce","year":"2014","journal-title":"Langmuir"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/0022-3093(89)90565-6","article-title":"Organic modification of glass structure, new glass or new polymer?","volume":"112","author":"Schmidt","year":"1989","journal-title":"J. Non-Cryst. Solids"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1007\/BF02436908","article-title":"Chemistry of hybrid organic-inorganic acess to silica materials through chemical selectivity","volume":"8","author":"Chevalier","year":"1997","journal-title":"J. Sol-Gel Sci. Technol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1021\/nn901146y","article-title":"In vivo biodistribution and clearance studies using multimodal organically modified silica nanoparticles","volume":"4","author":"Kumar","year":"2010","journal-title":"ACS Nano"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1128\/iai.17.2.274-277.1977","article-title":"Effect of silica on the pathogenic distinction between herpes simplex virus type 1 and 2 hepatitis in mice","volume":"17","author":"Mogensen","year":"1977","journal-title":"Infect. Immun."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"11539","DOI":"10.1073\/pnas.0504926102","article-title":"Organically modified silica nanoparticles: A nonviral vector for in vivo gene delivery and expression in the brain","volume":"102","author":"Bharali","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Barandeh, F., Nguyen, P.L., Kumar, R., Iacobucci, G.J., Kuznicki, M.L., Kosterman, A., Bergey, E.J., Prasad, P.N., and Gunawardena, S. (2012). Organically modified silica nanoparticles are biocompatible and can be targeted to neurons in vivo. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0029424"},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Wang, B., Hu, L., and Siahaan, T.J. (2016). Liposomes as Drug Delivery vehicles. Drug Delivery: Principles and Applications, Drug Discovery and Development, Wiley Series.","DOI":"10.1002\/9781118833322"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"599","DOI":"10.2174\/15734137113099990004","article-title":"Silica\/Ormosil SPIONs for biomedical applications","volume":"9","author":"Fortes","year":"2013","journal-title":"Curr. Nanosci."},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"B\u00e9gu, S., Pouessel, A.A., Lerner, D.A., Tourn\u00e9-P\u00e9teilh, C., and Devoisselle, J.-M. (2007). Liposil, a promising composite material for drug storage and realease. J. Control. Realese, 118.","DOI":"10.1016\/j.jconrel.2006.11.022"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1016\/j.optmat.2012.02.049","article-title":"Up-conversion in rare earth-doped silica hollow spheres","volume":"34","author":"Fortes","year":"2012","journal-title":"Opt. Mater."},{"key":"ref_151","unstructured":"Rodrigues, A.M., Gon\u00e7alves, M.C., Corvo, M.L., and Martins, M.B. (2017). Liposil as Nanocarriers for Pharmaceutical Applications: Process innovations. J. Nanomed. Nanotechnol., 8."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1038\/359710a0","article-title":"Ordered mesoporous molecular sieves synthesized by a liquid-crystal template mechanism","volume":"359","author":"Kresge","year":"1992","journal-title":"Nature"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/23\/8\/2021\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:18:31Z","timestamp":1760195911000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/23\/8\/2021"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,13]]},"references-count":152,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2018,8]]}},"alternative-id":["molecules23082021"],"URL":"https:\/\/doi.org\/10.3390\/molecules23082021","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,8,13]]}}}