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Hypoxia\u2010mediated chemoresistance remains a major hurdle for effective tumor chemotherapy. Herein, a new class of tLyP\u20101\u2010modified dopamine (DOPA)\u2010\u03b2\u2010cyclodextrin (CD)\u2010coated paclitaxel (PTX)\u2010 and manganese dioxide (MnO<jats:sub>2<\/jats:sub>)\u2010loaded nanoparticles (tLyP\u20101\u2010CD\u2010DOPA\u2010MnO<jats:sub>2<\/jats:sub>@PTX) is developed to enhance glioma chemotherapy. The nanomedicine delivered to the tumor site decomposes in response to the weak acidity and high hydrogen peroxide in the tumor microenvironment (TME), resulting in collapse of the system to release PTX and generates Mn<jats:sup>2+<\/jats:sup> and O<jats:sub>2<\/jats:sub>. In a rat model of intracranial glioma, tLyP\u20101\u2010CD\u2010DOPA\u2010MnO<jats:sub>2<\/jats:sub>@PTX can efficiently pass through the blood\u2010brain\u2010barrier to accumulate in tumor sites. The hypoxia in TME can be relieved via O<jats:sub>2<\/jats:sub> generated by MnO<jats:sub>2<\/jats:sub> and the reactive oxygen species produced by Mn<jats:sup>2+<\/jats:sup> can kill tumor cells. The tLyP\u20101\u2010CD\u2010DOPA\u2010MnO<jats:sub>2<\/jats:sub>@PTX nanoparticles exert a remarkable antitumor effect by promoting apoptosis and inhibiting proliferation of tumor cells in addition to enabling real\u2010time tumor monitoring with magnetic resonance imaging. This MnO<jats:sub>2<\/jats:sub>\u2010based theranostic medicine will offer a novel strategy to simultaneously enhance chemotherapy and achieve real\u2010time imaging of therapeutic process in glioma treatment.<\/jats:p>","DOI":"10.1002\/smtd.202101531","type":"journal-article","created":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T12:21:35Z","timestamp":1652962895000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Manganese Dioxide\u2010Based Nanocarrier Delivers Paclitaxel to Enhance Chemotherapy against Orthotopic Glioma through Hypoxia Relief"],"prefix":"10.1002","volume":"6","author":[{"given":"Shuqi","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Radiology Sun Yat\u2010Sen Memorial Hospital Sun Yat\u2010Sen University  Guangzhou 510120 China"},{"name":"Department of Radiology the First Affiliated Hospital of Guangzhou University of Chinese Medicine  Guangzhou 510405 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Radiology the First Affiliated Hospital of Anhui Medical University  Hefei 230022 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Radiology Sun Yat\u2010Sen Memorial Hospital Sun Yat\u2010Sen University  Guangzhou 510120 China"},{"name":"Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation  Guangzhou 510120 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaji","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Radiology Sun Yat\u2010Sen Memorial Hospital Sun Yat\u2010Sen University  Guangzhou 510120 China"},{"name":"Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation  Guangzhou 510120 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minghui","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Radiology Sun Yat\u2010Sen Memorial Hospital Sun Yat\u2010Sen University  Guangzhou 510120 China"},{"name":"Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation  Guangzhou 510120 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinna","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Radiology the First Affiliated Hospital of Anhui Medical University  Hefei 230022 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siming","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Radiology Sun Yat\u2010Sen Memorial Hospital Sun Yat\u2010Sen University  Guangzhou 510120 China"},{"name":"School of Pharmaceutical Sciences Guangzhou Medical University  Guangzhou 511436 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Radiology Sun Yat\u2010Sen Memorial Hospital Sun Yat\u2010Sen University  Guangzhou 510120 China"},{"name":"Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation  Guangzhou 510120 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7746-5285","authenticated-orcid":false,"given":"Jun","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Radiology Sun Yat\u2010Sen Memorial Hospital Sun Yat\u2010Sen University  Guangzhou 510120 China"},{"name":"Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation  Guangzhou 510120 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,5,19]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers3011129"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/cgt.2010.31"},{"key":"e_1_2_8_3_1","first-page":"2585","volume":"6","author":"Friedman H. 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