{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:15:39Z","timestamp":1787498139400,"version":"build-2736575974"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T00:00:00Z","timestamp":1599177600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T00:00:00Z","timestamp":1599177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Nanobiotechnol"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chemotherapy is a standard cancer treatment which uses anti-cancer drugs to destroy or slow the growth of cancer cells. However, chemotherapy has limited therapeutic effects in bladder cancer. One of the reasons of this resistance to chemotherapy is that higher levels of glutathione in invasive bladder cancer cells. We have fabricated nanoparticles that respond to high concentrations of glutathione and near-infrared laser irradiation in order to increase the drug accumulation at the tumor sites and combine chemotherapy with photothermal therapy to overcome the challenges of bladder cancer treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The DOX&amp;IR780@PEG-PCL-SS NPs were prepared by co-precipitation method. We investigated the tumor targeting capability of NPs in vitro and in vivo. The orthotopic bladder cancer model in C57BL\/6 mice was established for in vivo study and the photothermal effects and therapeutic efficacy of NPs were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The DOX&amp;IR780@PEG-PCL-SS NPs were synthesized using internal cross-linking strategy to increase the stability of nanoparticles. Nanoparticles can be ingested by tumor cells in a short time. The DOX&amp;IR780@PEG-PCL-SS NPs have dual sensitivity to high levels of glutathione in bladder cancer cells and near-infrared laser irradiation. Glutathione triggers chemical structural changes of nanoparticles and preliminarily releases drugs, Near-infrared laser irradiation can promote the complete release of the drugs from the nanoparticles and induce a photothermal effect, leading to destroying the tumor cells. Given the excellent tumor-targeting ability and negligible toxicity to normal tissue, DOX&amp;IR780@PEG-PCL-SS NPs can greatly increase the concentration of the anti-cancer drugs in tumor cells. The mice treated with DOX&amp;IR780@PEG-PCL-SS NPs have a significant reduction in tumor volume. The DOX&amp;IR780@PEG-PCL-SS NPs can be tracked by in vivo imaging system and have good tumor targeting ability, to facilitate our assessment during the experiment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>A nanoparticle delivery system with dual sensitivity to glutathione and near-infrared laser irradiation was developed for delivering IR780 and DOX. Chemo-photothermal synergistic therapy of both primary bladder cancer and their metastases was achieved using this advanced delivery system.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12951-020-00686-3","type":"journal-article","created":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T07:02:57Z","timestamp":1599202977000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Internal cross-linked polymeric nanoparticles with dual sensitivity for combination therapy of muscle-invasive bladder cancer"],"prefix":"10.1186","volume":"18","author":[{"given":"Guanchen","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaikai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haixiang","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaozhi","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linfeng","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenmin","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongqian","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,9,4]]},"reference":[{"issue":"2","key":"686_CR1","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.eururo.2012.07.033","volume":"63","author":"M Burger","year":"2013","unstructured":"Burger M, Catto JW, Dalbagni G, Grossman HB, Herr H, Karakiewicz P, et al. Epidemiology and risk factors of urothelial bladder cancer. Eur Urol. 2013;63(2):234\u201341.","journal-title":"Eur Urol"},{"issue":"4","key":"686_CR2","doi-asserted-by":"publisher","first-page":"990","DOI":"10.7150\/thno.22465","volume":"8","author":"T Lin","year":"2018","unstructured":"Lin T, Zhao X, Zhao S, Yu H, Cao W, Chen W, et al. O2-generating MnO2 nanoparticles for enhanced photodynamic therapy of bladder cancer by ameliorating hypoxia. Theranostics. 2018;8(4):990\u20131004.","journal-title":"Theranostics"},{"issue":"4","key":"686_CR3","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1016\/j.eururo.2013.11.046","volume":"65","author":"JA Witjes","year":"2014","unstructured":"Witjes JA, Comperat E, Cowan NC, De Santis M, Gakis G, Lebret T, et al. EAU guidelines on muscle-invasive and metastatic bladder cancer: summary of the 2013 guidelines. Eur Urol. 2014;65(4):778\u201392.","journal-title":"Eur Urol"},{"issue":"Suppl 3","key":"686_CR4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000052386","volume":"37","author":"KH Kurth","year":"2000","unstructured":"Kurth KH, Bouffioux C, Sylvester R, van der Meijden AP, Oosterlinck W, Brausi M. Treatment of superficial bladder tumors: achievements and needs. The EORTC Genitourinary Group. Eur Urol. 2000;37(Suppl 3):1\u20139.","journal-title":"Eur Urol"},{"issue":"1","key":"686_CR5","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.eururo.2016.06.010","volume":"71","author":"S Antoni","year":"2017","unstructured":"Antoni S, Ferlay J, Soerjomataram I, Znaor A, Jemal A, Bray F. Bladder cancer incidence and mortality: a global overview and recent trends. Eur Urol. 2017;71(1):96\u2013108.","journal-title":"Eur Urol"},{"issue":"35","key":"686_CR6","doi-asserted-by":"publisher","first-page":"5519","DOI":"10.1200\/JCO.2006.08.5431","volume":"24","author":"DJ Parekh","year":"2006","unstructured":"Parekh DJ, Bochner BH, Dalbagni G. Superficial and muscle-invasive bladder cancer: principles of management for outcomes assessments. J Clin Oncol. 2006;24(35):5519\u201327.","journal-title":"J Clin Oncol"},{"issue":"1","key":"686_CR7","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1021\/acsnano.5b00021","volume":"9","author":"JR Melamed","year":"2015","unstructured":"Melamed JR, Edelstein RS, Day ES. Elucidating the fundamental mechanisms of cell death triggered by photothermal therapy. ACS Nano. 2015;9(1):6\u201311.","journal-title":"ACS Nano"},{"issue":"3","key":"686_CR8","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1073\/pnas.72.3.937","volume":"72","author":"GM Hahn","year":"1975","unstructured":"Hahn GM, Braun J, Har-Kedar I. Thermochemotherapy: synergism between hyperthermia (42\u201343 degrees) and adriamycin (of bleomycin) in mammalian cell inactivation. Proc Natl Acad Sci USA. 1975;72(3):937\u201340.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"20","key":"686_CR9","doi-asserted-by":"publisher","first-page":"2731","DOI":"10.1002\/smll.201600365","volume":"12","author":"Z Li","year":"2016","unstructured":"Li Z, Wang H, Chen Y, Wang Y, Li H, Han H, et al. pH- and NIR light-responsive polymeric prodrug micelles for hyperthermia-assisted site-specific chemotherapy to reverse drug resistance in cancer treatment. Small. 2016;12(20):2731\u201340.","journal-title":"Small"},{"issue":"3","key":"686_CR10","doi-asserted-by":"publisher","first-page":"2056","DOI":"10.1021\/nn400334y","volume":"7","author":"M Zheng","year":"2013","unstructured":"Zheng M, Yue C, Ma Y, Gong P, Zhao P, Zheng C, et al. Single-step assembly of DOX\/ICG loaded lipid\u2013polymer nanoparticles for highly effective chemo-photothermal combination therapy. ACS Nano. 2013;7(3):2056\u201367.","journal-title":"ACS Nano"},{"issue":"7","key":"686_CR11","doi-asserted-by":"publisher","first-page":"948","DOI":"10.7150\/thno.15217","volume":"6","author":"P Zhang","year":"2016","unstructured":"Zhang P, Hu C, Ran W, Meng J, Yin Q, Li Y. Recent progress in light-triggered nanotheranostics for cancer treatment. Theranostics. 2016;6(7):948\u201368.","journal-title":"Theranostics"},{"key":"686_CR12","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1016\/j.actbio.2017.02.021","volume":"53","author":"T Lin","year":"2017","unstructured":"Lin T, Yuan A, Zhao X, Lian H, Zhuang J, Chen W, et al. Self-assembled tumor-targeting hyaluronic acid nanoparticles for photothermal ablation in orthotopic bladder cancer. Acta Biomater. 2017;53:427\u201338.","journal-title":"Acta Biomater"},{"issue":"9","key":"686_CR13","doi-asserted-by":"publisher","first-page":"2064","DOI":"10.1002\/1097-0142(19900501)65:9<2064::AID-CNCR2820650929>3.0.CO;2-2","volume":"65","author":"A Lafuente","year":"1990","unstructured":"Lafuente A, Giralt M, Cervello I, Pujol F, Mallol J. Glutathione-S-transferase activity in human superficial transitional cell carcinoma of the bladder. Comparison with healthy controls. Cancer. 1990;65(9):2064\u20138.","journal-title":"Cancer"},{"issue":"6","key":"686_CR14","doi-asserted-by":"publisher","first-page":"1452","DOI":"10.1016\/S0022-5347(17)36413-3","volume":"149","author":"M Giralt","year":"1993","unstructured":"Giralt M, Lafuente A, Pujol F, Mallol J. Enhanced glutathione s-transferase activity and glutathione content in human bladder cancer. Followup study: influence of smoking. J Urol. 1993;149(6):1452\u20134.","journal-title":"J Urol"},{"issue":"5","key":"686_CR15","doi-asserted-by":"publisher","first-page":"686","DOI":"10.3390\/cancers11050686","volume":"11","author":"A Loras","year":"2019","unstructured":"Loras A, Su\u00e1rez-Cabrera C, Mart\u00ednez-Bisbal MC, Quint\u00e1s G, Paramio JM, Mart\u00ednez-M\u00e1\u00f1ez R, et al. Integrative metabolomic and transcriptomic analysis for the study of bladder cancer. Cancers. 2019;11(5):686.","journal-title":"Cancers"},{"issue":"12","key":"686_CR16","doi-asserted-by":"publisher","first-page":"4185","DOI":"10.1002\/jps.24649","volume":"104","author":"L Zhang","year":"2015","unstructured":"Zhang L, Liu F, Li G, Zhou Y, Yang Y. Twin-arginine translocation peptide conjugated epirubicin-loaded nanoparticles for enhanced tumor penetrating and targeting. J Pharm Sci. 2015;104(12):4185\u201396.","journal-title":"J Pharm Sci"},{"issue":"6","key":"686_CR17","doi-asserted-by":"publisher","first-page":"2532","DOI":"10.1021\/acs.molpharmaceut.9b00132","volume":"16","author":"Y Zhao","year":"2019","unstructured":"Zhao Y, Zhao W, Lim YC, Liu T. Salinomycin-Loaded gold nanoparticles for treating cancer stem cells by ferroptosis-induced cell death. Mol Pharm. 2019;16(6):2532\u20139.","journal-title":"Mol Pharm"},{"issue":"28","key":"686_CR18","doi-asserted-by":"publisher","first-page":"6853","DOI":"10.1016\/j.biomaterials.2013.05.071","volume":"34","author":"C Yue","year":"2013","unstructured":"Yue C, Liu P, Zheng M, Zhao P, Wang Y, Ma Y, et al. IR-780 dye loaded tumor targeting theranostic nanoparticles for NIR imaging and photothermal therapy. Biomaterials. 2013;34(28):6853\u201361.","journal-title":"Biomaterials"},{"issue":"29","key":"686_CR19","doi-asserted-by":"publisher","first-page":"295603","DOI":"10.1088\/0957-4484\/22\/29\/295603","volume":"22","author":"G Gong","year":"2011","unstructured":"Gong G, Zhi F, Wang K, Tang X, Yuan A, Zhao L, et al. Fabrication of a nanocarrier system through self-assembly of plasma protein and its tumor targeting. Nanotechnology. 2011;22(29):295603.","journal-title":"Nanotechnology"},{"issue":"27","key":"686_CR20","doi-asserted-by":"publisher","first-page":"10980","DOI":"10.1073\/pnas.1106634108","volume":"108","author":"CM Hu","year":"2011","unstructured":"Hu CM, Zhang L, Aryal S, Cheung C, Fang RH, Zhang L. Erythrocyte membrane-camouflaged polymeric nanoparticles as a biomimetic delivery platform. Proc Natl Acad Sci USA. 2011;108(27):10980\u20135.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"3","key":"686_CR21","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1016\/j.xphs.2015.12.007","volume":"105","author":"K Wang","year":"2016","unstructured":"Wang K, Yuan A, Yu J, Wu J, Hu Y. One-step self-assembling method to prepare dual-functional transferrin nanoparticles for antitumor drug delivery. J Pharm Sci. 2016;105(3):1269\u201376.","journal-title":"J Pharm Sci"},{"issue":"1","key":"686_CR22","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1080\/10717544.2019.1639846","volume":"26","author":"Y Zhao","year":"2019","unstructured":"Zhao Y, Chen G, Meng Z, Gong G, Zhao W, Wang K, et al. A novel nanoparticle drug delivery system based on PEGylated hemoglobin for cancer therapy. Drug Deliv. 2019;26(1):717\u201323.","journal-title":"Drug Deliv"},{"key":"686_CR23","doi-asserted-by":"publisher","first-page":"27421","DOI":"10.1038\/srep27421","volume":"6","author":"K Wang","year":"2016","unstructured":"Wang K, Zhang Y, Wang J, Yuan A, Sun M, Wu J, et al. Self-assembled IR780-loaded transferrin nanoparticles as an imaging, targeting and PDT\/PTT agent for cancer therapy. Sci Rep. 2016;6:27421.","journal-title":"Sci Rep"},{"issue":"Pt A","key":"686_CR24","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1016\/j.jconrel.2015.11.017","volume":"220","author":"H Zhu","year":"2015","unstructured":"Zhu H, Zhang S, Ling Y, Meng G, Yang Y, Zhang W. pH-responsive hybrid quantum dots for targeting hypoxic tumor siRNA delivery. J Control Release. 2015;220(Pt A):529\u201344.","journal-title":"J Control Release"}],"container-title":["Journal of Nanobiotechnology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12951-020-00686-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12951-020-00686-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12951-020-00686-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,3]],"date-time":"2021-09-03T20:01:29Z","timestamp":1630699289000},"score":1,"resource":{"primary":{"URL":"https:\/\/jnanobiotechnology.biomedcentral.com\/articles\/10.1186\/s12951-020-00686-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,4]]},"references-count":24,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["686"],"URL":"https:\/\/doi.org\/10.1186\/s12951-020-00686-3","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-29953\/v1","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.3.rs-29953\/v3","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.3.rs-29953\/v2","asserted-by":"object"}]},"ISSN":["1477-3155"],"issn-type":[{"value":"1477-3155","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,4]]},"assertion":[{"value":"18 May 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 August 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 September 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All mice received care in terms of the guidelines for the Care and Use of Laboratory Animals and were used in terms of the Institutional Animal Care regulations and Use Committee (IACUC) of Nanjing University. All animal experiments were approved by the Administration Committee of Experimental Animals in Jiangsu Province and the Ethic Committee of Nanjing Drum Tower Hospital.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors have declared that no competing interest exists.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"124"}}