{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T12:16:51Z","timestamp":1788351411255,"version":"build-2803163510"},"reference-count":46,"publisher":"American Chemical Society (ACS)","issue":"12","license":[{"start":{"date-parts":[[2017,12,15]],"date-time":"2017-12-15T00:00:00Z","timestamp":1513296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"funder":[{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology , Ministry of Science and Technology","doi-asserted-by":"publisher","award":["DBT\/CHE\/20100304"],"award-info":[{"award-number":["DBT\/CHE\/20100304"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,12,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\u03b2-Galactosidase (\u03b2-gal) is one of the important lysosomal enzymes that is involved in the breakdown of glycosphingolipids (e.g., GM1 ganglioside), and its deficiency leads to GM1 Gangliosidosis, a lysosomal storage disorder (LSD). Intracellular delivery of \u03b2-gal is one of the preferable methods to treat this kind of LSDs. However, it cannot permeate the cell membrane due to its intricate macromolecular nature, low stability, and degradation by endogenous proteases. To this end, we report efficient intracellular delivery of \u03b2-gal via arginase-responsive dextran sulfate\/poly-l-arginine polymer capsules (DS\/PA capsules). The therapeutic activity of \u03b2-gal enzyme has been assessed in two gene-deficient diseased cell lines, SV (\u03b2-galactosidase gene-deficient mouse fibroblast) and R201C (deficient human \u03b2-galactosidase gene-introduced mouse fibroblast), and in wild-type mouse fibroblast immortalized cell lines. The activity of \u03b2-gal enzyme has been estimated within cells by using fluorescein isothiocyanate-cholera toxin B as a florescent probe that illustrates the level of GM1 ganglioside, the \u03b2-gal substrate. We found 1.8-, 3.4-, and 2.8-fold reduction in the substrate level in R201C, SV, and wild-type mouse fibroblast, respectively, which confirms the release and therapeutic activity of \u03b2-gal enzyme inside the cells. Moreover, enzyme delivery in gene-deficient diseased cell lines (SV and R201C) via DS\/PA capsules reduced the level of enzyme substrate to a normal endogenous level, which is present in untreated wild-type mouse fibroblast cells. We note that loading of \u03b2-gal enzyme within DS\/PA capsules was estimated to be 3 mU per hundred capsules and more than 77% of \u03b2-gal is released within 12 h. Overall, these results highlight the potential of DS\/PA capsules as an efficient delivery carrier for therapeutic enzyme.<\/jats:p>","DOI":"10.1021\/acsomega.7b01230","type":"journal-article","created":{"date-parts":[[2017,12,15]],"date-time":"2017-12-15T09:03:45Z","timestamp":1513328625000},"page":"9002-9012","source":"Crossref","is-referenced-by-count":15,"title":["Intracellular Delivery of \u03b2-Galactosidase\nEnzyme Using Arginase-Responsive Dextran Sulfate\/Poly-\n                    <scp>l<\/scp>\n                    -arginine Capsule for Lysosomal Storage Disorder"],"prefix":"10.1021","volume":"2","author":[{"given":"Meenakshi","family":"Gupta","sequence":"first","affiliation":[{"name":"Chhatrapati Shahu Ji Maharaj University , , , ,","place":["Kanpur, Uttar Pradesh, India, 208024"]},{"name":"Sam Higginbottom University of Agriculture, Technology and Sciences , , , ,","place":["Allahabad, Uttar Pradesh, India, 211007"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Himanshu","family":"Pandey","sequence":"additional","affiliation":[{"name":"Sam Higginbottom University of Agriculture, Technology and Sciences , , , ,","place":["Allahabad, Uttar Pradesh, India, 211007"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6472-2702","authenticated-orcid":true,"given":"Sri","family":"Sivakumar","sequence":"additional","affiliation":[{"name":"Indian Institute of Technology Kanpur , , , ,","place":["Kanpur, Uttar Pradesh, India, 208016"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2017,12,15]]},"reference":[{"key":"2026090207320949400_cit1","doi-asserted-by":"publisher","first-page":"10195","DOI":"10.1523\/JNEUROSCI.0822-13.2013","article-title":"Gangliosides and Gangliosidoses: Principles of Molecular\nand Metabolic Pathogenesis","volume":"33","author":"Sandhoff","year":"2013","journal-title":"J. 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Lipid\nRes."},{"key":"2026090207320949400_cit5","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.ymgme.2008.02.005","article-title":"Beneficial effects of substrate reduction\ntherapy in a mouse model of GM1 gangliosidosis","volume":"94","author":"Elliot-Smith","year":"2008","journal-title":"Mol. Genet. Metab."},{"key":"2026090207320949400_cit6","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1098\/rstb.2003.1279","article-title":"Substrate\nreduction therapy in mouse models of the\nglycosphingolipidoses","volume":"358","author":"Platt","year":"2003","journal-title":"Philos. Trans. R. Soc.,\nB"},{"key":"2026090207320949400_cit7","doi-asserted-by":"publisher","first-page":"145","DOI":"10.2183\/pjab.90.145","article-title":"Emerging novel\nconcept of chaperone therapies for protein misfolding diseases","volume":"90","author":"Suzuki","year":"2014","journal-title":"Proc. Jpn. Acad., Ser. 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Pharm."},{"key":"2026090207320949400_cit28","doi-asserted-by":"publisher","first-page":"1283","DOI":"10.1021\/bm101559w","article-title":"Encapsulation\nperformance of layer-by-layer microcapsules for proteins","volume":"12","author":"De Temmerman","year":"2011","journal-title":"Biomacromolecules"},{"key":"2026090207320949400_cit29","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1016\/j.addr.2011.03.016","article-title":"Layer-by-layer\nself-assembled shells for drug delivery","volume":"63","author":"Ariga","year":"2011","journal-title":"Adv.\nDrug Delivery Rev."},{"key":"2026090207320949400_cit30","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.3390\/polym7071269","article-title":"pH-Dependent\nrelease of insulin from layer-by-layer-deposited polyelectrolyte microcapsules","volume":"7","author":"Yoshida","year":"2015","journal-title":"Polymers"},{"key":"2026090207320949400_cit31","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/S1389-1723(99)80010-3","article-title":"Activity and\nstability of glucose\noxidase in molecular films assembled alternately with polyions","volume":"87","author":"Onda","year":"1999","journal-title":"J. Biosci. Bioeng."},{"key":"2026090207320949400_cit32","doi-asserted-by":"publisher","first-page":"203","DOI":"10.4049\/jimmunol.0803591","article-title":"Biodegradable Polyelectrolyte\nMicrocapsules: Antigen Delivery Tools with Th17 Skewing Activity after\nPulmonary Delivery","volume":"184","author":"De Koker","year":"2010","journal-title":"J. Immunol."},{"key":"2026090207320949400_cit33","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1021\/bp0495825","article-title":"Protein\u2500Calcium\nCarbonate\nCoprecipitation: A Tool for Protein Encapsulation","volume":"21","author":"Petrov","year":"2005","journal-title":"Biotechnol. Prog."},{"key":"2026090207320949400_cit34","doi-asserted-by":"publisher","first-page":"3398","DOI":"10.1021\/la036177z","article-title":"Matrix\npolyelectrolyte microcapsules: new system for macromolecule encapsulation","volume":"20","author":"Volodkin","year":"2004","journal-title":"Langmuir"},{"key":"2026090207320949400_cit35","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1002\/adma.200502128","article-title":"Intracellularly Degradable Polyelectrolyte Microcapsules","volume":"18","author":"De Geest","year":"2006","journal-title":"Adv. Mater."},{"key":"2026090207320949400_cit36","doi-asserted-by":"publisher","first-page":"3687","DOI":"10.1002\/adma.200800907","article-title":"Self-Exploding Beads\nReleasing Microcarriers","volume":"20","author":"De Geest","year":"2008","journal-title":"Adv. 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Basica Apl."},{"key":"2026090207320949400_cit40","first-page":"177","article-title":"Magnesium chelation inactivates beta-galactosidase\nin-20 degrees C storage","volume":"12","author":"Lu","year":"1992","journal-title":"Biotechniques"},{"key":"2026090207320949400_cit41","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1111\/j.1574-6968.2006.00545.x","article-title":"Rafting with cholera\ntoxin: endocytosis and trafficking from plasma membrane to ER","volume":"266","author":"Chinnapen","year":"2007","journal-title":"FEMS Microbiol. Lett."},{"key":"2026090207320949400_cit42","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1038\/sj.icb.7100045","article-title":"Cholera toxin binds\nto lipid rafts but has a limited\nspecificity for ganglioside GM1","volume":"85","author":"Blank","year":"2007","journal-title":"Immunol. Cell\nBiol."},{"key":"2026090207320949400_cit43","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.ymgme.2015.12.002","article-title":"Enzyme\nreplacement for GM1-gangliosidosis: Uptake, lysosomal activation,\nand cellular disease correction using a novel \u03b2-galactosidase:\nRTB lectin fusion","volume":"117","author":"Condori","year":"2016","journal-title":"Mol. Genet. Metab."},{"key":"2026090207320949400_cit44","doi-asserted-by":"publisher","first-page":"15635","DOI":"10.1039\/C5NR04361A","article-title":"A novel fluorescent retrograde neural\ntracer: cholera toxin B conjugated carbon dots","volume":"7","author":"Zhou","year":"2015","journal-title":"Nanoscale"},{"key":"2026090207320949400_cit45","doi-asserted-by":"publisher","first-page":"12391","DOI":"10.1073\/pnas.221181998","article-title":"Accumulation\nof cholera toxin and\nGM1 ganglioside in the early endosome of Niemann\u2013Pick C1-deficient\ncells","volume":"98","author":"Sugimoto","year":"2001","journal-title":"Proc. Natl. Acad. Sci. 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