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Pro\u2010THPC could be activated by glutathione (GSH) to release the dual\u2010sensitizer, THPC, which simultaneously switches on fluorescence emission and combined capabilities of photodynamic therapy (PDT) and sonodynamic therapy (SDT). Pro\u2010THPC is further formulated into nanoparticles (NPs) for water dispersity to enable in vivo applications. In vivo fluorescence imaging shows that the pro\u2010THPC NPs group exhibits a significantly higher tumor\u2010to\u2010normal tissue ratio (\n                    <jats:italic>T<\/jats:italic>\n                    \/\n                    <jats:italic>N<\/jats:italic>\n                    ) (\n                    <jats:italic>T<\/jats:italic>\n                    \/\n                    <jats:italic>N<\/jats:italic>\n                    = 5.2 \u00b1 0.55) compared to the \u201calways on\u201d THPC NPs group (\n                    <jats:italic>T<\/jats:italic>\n                    \/\n                    <jats:italic>N<\/jats:italic>\n                    = 2.9 \u00b1 0.47) and the pro\u2010THPC NPs group co\u2010administrated with GSH synthesis inhibitor (buthionine sulfoximine, BSO) (\n                    <jats:italic>T<\/jats:italic>\n                    \/\n                    <jats:italic>N<\/jats:italic>\n                    = 3.2 \u00b1 0.63). In addition, the generation of the designed dual\u2010sensitizer's reactive oxygen species (ROS) is effectively confined within the tumor tissues due to the relatively strong correlation between ROS generation and fluorescence emission. In vivo studies further demonstrate the remarkable efficacy of the designed pro\u2010THPC NPs to eradicate tumors through the combination of PDT and SDT while significantly reducing skin phototoxicity.\n                  <\/jats:p>","DOI":"10.1002\/smll.202400667","type":"journal-article","created":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T03:01:45Z","timestamp":1717556505000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["A GSH\u2010Responsive Prodrug with Simultaneous Triple\u2010Activation Capacity for Photodynamic\/Sonodynamic Combination Therapy with Inhibited Skin Phototoxicity"],"prefix":"10.1002","volume":"20","author":[{"given":"Caiting","family":"Deng","sequence":"first","affiliation":[{"name":"Institute of Medical Engineering School of Basic Medical Science Health Science Center Xi'an Jiaotong University  No. 76 Yanta West Road Xi'an Shaanxi 710061 China"},{"name":"School of Public Health Health Science Center Xi'an Jiaotong University  No.76 Yanta West Road Xi'an Shaanxi 710061 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Public Health Health Science Center Xi'an Jiaotong University  No.76 Yanta West Road Xi'an Shaanxi 710061 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanchun","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Public Health Health Science Center Xi'an Jiaotong University  No.76 Yanta West Road Xi'an Shaanxi 710061 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shupeng","family":"Han","sequence":"additional","affiliation":[{"name":"School of Public Health Health Science Center Xi'an Jiaotong University  No.76 Yanta West Road Xi'an Shaanxi 710061 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