{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T12:18:51Z","timestamp":1772799531380,"version":"3.50.1"},"reference-count":37,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2018,11,28]],"date-time":"2018-11-28T00:00:00Z","timestamp":1543363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science &amp; Technology Specific Projects","award":["2015ZX09J15104-003-003"],"award-info":[{"award-number":["2015ZX09J15104-003-003"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["21471046 and 81603062"],"award-info":[{"award-number":["21471046 and 81603062"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Dimercaptosuccinic acid (DMSA) is an oral heavy metal chelator. Although DMSA is the most acceptable chelator in the urinary excretion of toxic elements from children and adults, its defects in plasma binding and the membrane permeability limit its interaction with intracellular elements and affect its efficacy in chelation therapy. Herein, a novel nanocomposite composed of mesoporous silica nanoparticles (MSNs), disulfide bond, and DMSA was synthesized and characterized with a scanning\/transmission electron microscope, IR and Raman spectra, and TGA analysis. The in vitro interactions with glutathione (GSH) and cellular uptake assays showed that it was able to be stable in extracellular environments such as in blood, be internalized by cells, and release DMSA inside via GSH-triggered disulfide cleavage reaction. The in vitro adsorption assays showed that MSNs-SH as its intracellular metabolite had strong adsorbability for models of Hg2+ or Pb2+. The hemolysis and cell viability assays showed that it was compatible with blood and cells even at a concentration of 1000 \u03bcg\u00b7mL\u22121. All above could not only enable it to be a GSH-responsive drug delivery system (DDS) for DMSA delivery but also to be a solution for its defects and efficacy. Thus, introduction of intelligent DDS might open a new avenue for DMSA-based chelation therapy.<\/jats:p>","DOI":"10.3390\/ijms19123790","type":"journal-article","created":{"date-parts":[[2018,11,28]],"date-time":"2018-11-28T11:43:44Z","timestamp":1543405424000},"page":"3790","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Construction of a Glutathione-Responsive and Silica-Based Nanocomposite for Controlled Release of Chelator Dimercaptosuccinic Acid"],"prefix":"10.3390","volume":"19","author":[{"given":"Hongqiang","family":"Zhai","sequence":"first","affiliation":[{"name":"College of Pharmacy, Institutes of Environment and Medicine, Henan University, Kaifeng 475004, China"},{"name":"Institute of Medicinal Biotechnology of Medical Science &amp; Peking Union Medical College, Beijing 100850, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuli","family":"Wang","sequence":"additional","affiliation":[{"name":"State key laboratory of toxicology and medical countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Menghua","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Institutes of Environment and Medicine, Henan University, Kaifeng 475004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuai","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Institutes of Environment and Medicine, Henan University, Kaifeng 475004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feifei","family":"Yu","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Biotechnology of Medical Science &amp; Peking Union Medical College, Beijing 100850, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunsheng","family":"Gao","sequence":"additional","affiliation":[{"name":"State key laboratory of toxicology and medical countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guiling","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Biotechnology of Medical Science &amp; Peking Union Medical College, Beijing 100850, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiang","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Institutes of Environment and Medicine, Henan University, Kaifeng 475004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Tchounwou, P.B., Yedjou, C.G., Patlolla, A.K., and Sutton, D.J. (2012). Heavy Metal Toxicity and the Environment, Springer.","DOI":"10.1007\/978-3-7643-8340-4_6"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Sears, M.E. (2013). Chelation: Harnessing and Enhancing Heavy Metal Detoxification\u2014A Review. The Scientific World J., 2013.","DOI":"10.1155\/2013\/219840"},{"key":"ref_3","unstructured":"Naranjan, S.D. (2001). Molecular Mechanisms of Metal Toxicity and Carcinogenesis, Kluwer Academic Publishers."},{"key":"ref_4","unstructured":"Mukesh, V. (2009). Lung Cancer and Exposure to Metals: The Epidemiological Evidence, Humana Press."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1146\/annurev.pa.23.040183.001205","article-title":"DMSA and DMPS\u2014Water soluble antidotes for heavy metal poisoning","volume":"23","author":"Aposhian","year":"1983","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_6","first-page":"734","article-title":"Metabolism of meso-2,3-dimercaptosuccinic acid in lead-poisoned children and normal adults","volume":"103","author":"Asiedu","year":"1995","journal-title":"Environ. Health Perspect."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1080\/15563650903174828","article-title":"Dimercaptosuccinic acid (succimer; DMSA) in inorganic lead poisoning","volume":"47","author":"Bradberry","year":"2009","journal-title":"Clin. Toxicol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1385\/BTER:83:3:207","article-title":"EDTA chelation effects on urinary losses of cadmium, calcium, chromium, cobalt, copper, lead, magnesium, and zinc","volume":"83","author":"Waters","year":"2001","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2749","DOI":"10.1021\/am100616b","article-title":"Functionalized Nanoporous Silica for Removal of Heavy Metals from Biological Systems; Adsorption and Application","volume":"2","author":"Yantasee","year":"2010","journal-title":"ACS Appl. Mat. Inter."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/BF02795598","article-title":"Chelation in metal intoxication XXVI","volume":"14","author":"Kachru","year":"1987","journal-title":"Biolog. Trace Elem. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1021\/tx200155g","article-title":"Lead Detoxification Activities of a Class of Novel DMSA\u2013Amino Acid Conjugates","volume":"24","author":"Xu","year":"2011","journal-title":"Chem. Res. Toxicol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"8373","DOI":"10.1002\/anie.201203993","article-title":"Functional Mesoporous Silica Nanoparticles for Photothermal-Controlled Drug Delivery In Vivo","volume":"51","author":"Yan","year":"2012","journal-title":"Angew. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"19582","DOI":"10.1021\/ja206998x","article-title":"Bioresponsive Mesoporous Silica Nanoparticles for Triggered Drug Release","volume":"133","author":"Neetu","year":"2011","journal-title":"J. Am. Chem. Soc."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1021\/ja807798g","article-title":"Light-operated mechanized nanoparticles","volume":"131","author":"Ferris","year":"2009","journal-title":"J. Am. Chem. Soc."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"14418","DOI":"10.1021\/ja8060886","article-title":"Tunable redox-responsive hybrid nanogated ensembles","volume":"130","author":"Liu","year":"2008","journal-title":"J. Am. Chem. Soc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1002\/anie.200603404","article-title":"Controlled release of guest molecules from mesoporous silica particles based on a pH-responsive polypseudorotaxane motif","volume":"46","author":"Park","year":"2007","journal-title":"Angew. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6353","DOI":"10.1021\/nn101499d","article-title":"Enzyme-responsive intracellular controlled release using nanometric silica mesoporous supports capped with \u201csaccharides\u201d","volume":"4","author":"Bernardos","year":"2010","journal-title":"ACS Nano"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4764","DOI":"10.1039\/b902985k","article-title":"Magnetic mesoporous silica microspheres with thermo-sensitive polymer shell for controlled drug release","volume":"19","author":"Liu","year":"2009","journal-title":"J. Mater. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"14075","DOI":"10.1021\/ja904456d","article-title":"Controlled delivery systems using antibody-capped mesoporous nanocontainers","volume":"131","author":"Climent","year":"2009","journal-title":"J. Am. Chem. Soc."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"8398","DOI":"10.1021\/ja901831u","article-title":"Mesoporous silica nanoparticle-based double drug delivery system for glucose-responsive controlled release of insulin and cyclic AMP","volume":"131","author":"Zhao","year":"2009","journal-title":"J. Am. Chem. Soc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3144","DOI":"10.1002\/adma.201205292","article-title":"In vivo bio-safety evaluations and diagnostic\/therapeutic applications of chemically designed mesoporous silica nanoparticles","volume":"25","author":"Chen","year":"2013","journal-title":"Adv. Mater."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"16869","DOI":"10.1039\/c1jm11869b","article-title":"Multifunctional mesoporous silica nanocomposite nanoparticles for pH controlled drug release and dual modal imaging","volume":"21","author":"Ji","year":"2011","journal-title":"J. Mater. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1002\/smll.201001459","article-title":"In vivo Biodistribution and Urinary Excretion of Mesoporous Silica Nanoparticles: Effects of Particle Size and PEGylation","volume":"7","author":"He","year":"2011","journal-title":"Small"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5071","DOI":"10.1021\/cr300358b","article-title":"Disulfide-cleavage-triggered chemosensors and their biological applications","volume":"113","author":"Min","year":"2013","journal-title":"Chem. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1002\/adhm.201400726","article-title":"\u03b3-PGA-Coated Mesoporous Silica Nanoparticles with Covalently Attached Prodrugs for Enhanced Cellular Uptake and Intracellular GSH-Responsive Release","volume":"4","author":"Du","year":"2015","journal-title":"Adv. Healthc. Mater."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"14210","DOI":"10.1039\/c3cp51947c","article-title":"A reduction-sensitive carrier system using mesoporous silica nanospheres with biodegradable polyester as caps","volume":"15","author":"Hongyan","year":"2013","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/S1001-0742(07)60026-6","article-title":"Removal of heavy metals from aqueous solution by sawdust adsorption","volume":"19","author":"Bulut","year":"2007","journal-title":"J. Environ. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1016\/j.polymer.2014.01.043","article-title":"Thiol-modified cellulose nanofibrous composite membranes for chromium (VI) and lead (II) adsorption","volume":"55","author":"Yang","year":"2014","journal-title":"Polymer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.apsusc.2013.11.156","article-title":"Magnetic ion-imprinted and \u2013SH functionalized polymer for selective removal of Pb(II) from aqueous samples","volume":"292","author":"Guo","year":"2014","journal-title":"Appl. Surf. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"385101","DOI":"10.1088\/0957-4484\/26\/38\/385101","article-title":"A novel route for the removal of bodily heavy metal lead (II)","volume":"26","author":"Huang","year":"2015","journal-title":"Nanotechnology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"21750","DOI":"10.1021\/am507602v","article-title":"Correctionto Novel Oral Detoxification of Mercury, Cadmium, and Lead with Thiol-Modified Nanoporous Silica","volume":"6","author":"Sangvanich","year":"2014","journal-title":"ACS Appl. Mat. Inter."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2800","DOI":"10.1039\/C5RA17517H","article-title":"Implications for blood-brain-barrier permeability, in vitro oxidative stress and neurotoxicity potential induced by mesoporous silica nanoparticles: Effects of surface modification","volume":"6","author":"Zhou","year":"2015","journal-title":"RSC Adv."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"7486","DOI":"10.1039\/c3ra00095h","article-title":"Fabrication of heparinized hierarchically hollow hydroxyapatite microspheres as bone substitute for controlled growth factors delivery","volume":"3","author":"Wu","year":"2013","journal-title":"RSC Adv."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.micromeso.2008.08.004","article-title":"Size-controlled synthesis of monodispersed mesoporous silica nano-spheres under a neutral condition","volume":"117","author":"He","year":"2009","journal-title":"Microporous Mesoporous Mater."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"9937","DOI":"10.1021\/acsami.5b02131","article-title":"Functionalised Mesoporous Silica Nanoparticles with Redox Responsive Short-Chain Gatekeepers for Agrochemical Delivery","volume":"7","author":"Yi","year":"2015","journal-title":"ACS Appl. Mater. Inter."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"14983","DOI":"10.1021\/acsami.5b03873","article-title":"Sulfhydryl-Modified Fe3O4@SiO2 Core\/Shell Nanocomposite: Synthesis and Toxicity Assessment in Vitro","volume":"7","author":"Guo","year":"2015","journal-title":"ACS Appl. Mater. Inter."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"485703","DOI":"10.1088\/0957-4484\/23\/48\/485703","article-title":"Heparinized magnetic mesoporous silica nanoparticles as multifunctional growth factor delivery carriers","volume":"23","author":"Wu","year":"2012","journal-title":"Nanotechnology"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/12\/3790\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:33:07Z","timestamp":1760196787000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/12\/3790"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,28]]},"references-count":37,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["ijms19123790"],"URL":"https:\/\/doi.org\/10.3390\/ijms19123790","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,28]]}}}