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Herein, a reduction-responsive sulfur dioxide (SO\n                    <jats:sub>2<\/jats:sub>\n                    ) polymer prodrug was synthesized as a nanocarrier to load irinotecan (IRN) to be used in combination osteosarcoma therapy. The SO\n                    <jats:sub>2<\/jats:sub>\n                    prodrug (denoted as mPEG-PLG (DNs)) was synthesized by coupling a small-molecule SO\n                    <jats:sub>2<\/jats:sub>\n                    donor,\n                    <jats:italic>N<\/jats:italic>\n                    -(3-azidopropyl)-2,4-dinitrobenzenesulfonamide (AP-DNs), to the side chains of methoxy poly (ethylene glycol)-\n                    <jats:italic>block<\/jats:italic>\n                    -poly (\u03b3-propargyl-\n                    <jats:sub>L<\/jats:sub>\n                    -glutamate) block copolymer. The mPEG-PLG (DNs) had the ability to self-assemble into micelles while simultaneously encapsulating IRN in aqueous media. The formed micelles led to enhanced SO\n                    <jats:sub>2<\/jats:sub>\n                    and IRN release in reductive conditions. Using nile red as a model drug, the loaded micelles were efficiently internalized by cancer cells, demonstrated by confocal laser scanning microscopy and flow cytometry. The release of SO\n                    <jats:sub>2<\/jats:sub>\n                    within nanoparticles (NPs) in tumor cells led to enhanced intracellular reactive oxygen species amounts together with induced oxidative destruction to cancer cells. Furthermore, the IRN-loaded SO\n                    <jats:sub>2<\/jats:sub>\n                    polymer prodrug NPs mediated synergistic therapeutic effects against osteosarcoma cells, leading to improved biodistribution and enhanced tumor growth inhibition over control groups in a murine osteosarcoma model. Taken together, this work highlights the potential of SO\n                    <jats:sub>2<\/jats:sub>\n                    polymer prodrugs as reduction-responsive nanocarriers to load chemotherapeutics for effective combination osteosarcoma therapy.\n                  <\/jats:p>","DOI":"10.1088\/1361-6528\/aba783","type":"journal-article","created":{"date-parts":[[2020,7,20]],"date-time":"2020-07-20T18:16:30Z","timestamp":1595268990000},"page":"455101","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Reduction-responsive sulfur dioxide polymer prodrug nanoparticles loaded with irinotecan for combination osteosarcoma therapy"],"prefix":"10.1088","volume":"31","author":[{"given":"Yongshuang","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junxing","family":"Qu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8594-9770","authenticated-orcid":false,"given":"Zhiyu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"266","published-online":{"date-parts":[[2020,8,14]]},"reference":[{"key":"nanoaba783bib1","doi-asserted-by":"publisher","first-page":"1500","DOI":"10.1093\/annonc\/mdu153","type":"journal-article","article-title":"ENCCA WP17-WP7 consensus paper on teenagers and young adults (TYA) with bone sarcomas","volume":"25","author":"Wilhelm","year":"2014","journal-title":"Ann. 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All rights, including for text and data mining, AI training, and similar technologies, are reserved.","name":"copyright_information","label":"Copyright Information"},{"value":"2020-05-06","name":"date_received","label":"Date Received","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2020-07-20","name":"date_accepted","label":"Date Accepted","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2020-08-14","name":"date_epub","label":"Online publication date","group":{"name":"publication_dates","label":"Publication dates"}}]}}