{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T20:19:00Z","timestamp":1789676340842,"version":"4.0.1"},"reference-count":26,"publisher":"IOP Publishing","issue":"29","license":[{"start":{"date-parts":[[2020,5,5]],"date-time":"2020-05-05T00:00:00Z","timestamp":1588636800000},"content-version":"vor","delay-in-days":4,"URL":"https:\/\/publishingsupport.iopscience.iop.org\/iop-standard\/v1"},{"start":{"date-parts":[[2020,5,5]],"date-time":"2020-05-05T00:00:00Z","timestamp":1588636800000},"content-version":"tdm","delay-in-days":4,"URL":"https:\/\/iopscience.iop.org\/info\/page\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"crossref","award":["19XD1420200"],"award-info":[{"award-number":["19XD1420200"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81673018"],"award-info":[{"award-number":["81673018"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["iopscience.iop.org"],"crossmark-restriction":false},"short-container-title":["Nanotechnology"],"published-print":{"date-parts":[[2020,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Despite the promising target of immunosuppressive enzyme indoleamine-2,3-dioxygenase (IDO) for cancer immunotherapy, IDO blockade monotherapy does not show significant benefit to cancer patients in the clinic. Recent research has focused on the combinatorial therapy of the IDO inhibitor and the immune checkpoint blockade or chemotherapy. Here, we synthesize a drug conjugate methyltryptophan-paclitaxel (MP) by linking the IDO inhibitor, D-1-methyltryptophan (D-1MT), to the chemotherapeutic agent, paclitaxel (PTX), through an ester bond. MP exhibits a similar tubulin-stabilizing effect to PTX. Like PTX, MP binds to human serum albumin to form albumin-bound MP nanoparticles (MP NPs) with a particle size of \u223c115 nm in diameter. MP NPs significantly improve the tumor concentration of D-1MT due to the hydrolysis of MP in tumors. The codelivery of PTX and D-1MT offered by MP NPs in tumors significantly enhances the anti-tumor effect compared with the albumin-bound PTX NPs. Immune cell phenotyping reveals that MP NPs ameliorate the immune environment through increasing the number of the effector CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, and decreasing the population of regulatory T cells and granulocyte-like myeloid-derived suppressor cells. These results prove that the design of the twin drug from the IDO inhibitor and PTX synergizes the anti-tumor effect and shows promise in clinical translation.\n                  <\/jats:p>","DOI":"10.1088\/1361-6528\/ab824d","type":"journal-article","created":{"date-parts":[[2020,3,23]],"date-time":"2020-03-23T18:15:24Z","timestamp":1584987324000},"page":"295101","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":23,"title":["An albumin-bound drug conjugate of paclitaxel and indoleamine-2,3-dioxygenase inhibitor for enhanced cancer chemo-immunotherapy"],"prefix":"10.1088","volume":"31","author":[{"given":"Zihua","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binbin","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaojiao","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1333-0274","authenticated-orcid":false,"given":"Wei","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"266","published-online":{"date-parts":[[2020,5,5]]},"reference":[{"key":"nanoab824dbib1","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1038\/nm934","type":"journal-article","article-title":"Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase","volume":"9","author":"Uyttenhove","year":"2003","journal-title":"Nat. Med."},{"key":"nanoab824dbib2","doi-asserted-by":"publisher","first-page":"1598","DOI":"10.3389\/fimmu.2018.01598","type":"journal-article","article-title":"Indoleamine 2,3-dioxygenase expression pattern in the tumor microenvironment predicts clinical outcome in early stage cervical cancer","volume":"9","author":"Heeren","year":"2018","journal-title":"Front. Immunol."},{"key":"nanoab824dbib3","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1016\/S0167-5699(99)01520-0","type":"journal-article","article-title":"Tryptophan catabolism and T-cell tolerance: immunosuppression by starvation?","volume":"20","author":"Mellor","year":"1999","journal-title":"Immunol. Today"},{"key":"nanoab824dbib4","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1038\/nm1196","type":"journal-article","article-title":"Inhibition of indoleamine 2,3-dioxygenase, an immunoregulatory target of the cancer suppression gene Bin1, potentiates cancer chemotherapy","volume":"11","author":"Muller","year":"2005","journal-title":"Nat. Med."},{"key":"nanoab824dbib5","doi-asserted-by":"publisher","first-page":"4782","DOI":"10.1111\/febs.12444","type":"journal-article","article-title":"The expanding roles of 1-methyl-tryptophan (1-Mt): in addition to inhibiting kynurenine production, 1-Mt activates the synthesis of melatonin in skin cells","volume":"280","author":"Moreno","year":"2013","journal-title":"FEBS J."},{"key":"nanoab824dbib6","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1158\/0008-5472.CAN-06-2925","type":"journal-article","article-title":"Inhibition of indoleamine 2,3-dioxygenase in dendritic cells by stereoisomers of 1-methyl-tryptophan correlates with antitumor responses","volume":"67","author":"Hou","year":"2007","journal-title":"Cancer Res."},{"key":"nanoab824dbib7","doi-asserted-by":"publisher","first-page":"370","DOI":"10.3389\/fonc.2018.00370","type":"journal-article","article-title":"Indoximod: an immunometabolic adjuvant that empowers T cell activity in cancer","volume":"8","author":"Fox","year":"2018","journal-title":"Front. Oncol."},{"key":"nanoab824dbib8","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1007\/s40259-018-0291-4","type":"journal-article","article-title":"Indoleamine 2,3-dioxygenase (IDO) inhibition as a strategy to augment cancer immunotherapy","volume":"32","author":"Yentz","year":"2018","journal-title":"BioDrugs"},{"key":"nanoab824dbib9","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1080\/13543776.2018.1441290","type":"journal-article","article-title":"A patent review of IDO1 inhibitors for cancer","volume":"28","author":"Cheong","year":"2018","journal-title":"Expert. Opin. Ther. Pat."},{"key":"nanoab824dbib10","doi-asserted-by":"publisher","first-page":"9512","DOI":"10.1200\/JCO.2018.36.15_suppl.9512","type":"journal-article","article-title":"Phase 2 trial of the IDO pathway inhibitor indoximod plus checkpoint inhibition for the treatment of patients with advanced melanoma","volume":"36","author":"Zakharia","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"nanoab824dbib11","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13443","type":"journal-article","article-title":"An immunostimulatory dual-functional nanocarrier that improves cancer immunochemotherapy","volume":"7","author":"Chen","year":"2016","journal-title":"Nat. Commun."},{"key":"nanoab824dbib12","doi-asserted-by":"publisher","first-page":"14854","DOI":"10.1021\/jacs.5b10182","type":"journal-article","article-title":"A Pt(IV) pro-drug preferentially targets indoleamine-2,3-dioxygenase, providing enhanced ovarian cancer immuno-chemotherapy","volume":"137","author":"Awuah","year":"2015","journal-title":"J. Am. Chem. Soc."},{"key":"nanoab824dbib13","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2019.105034","type":"journal-article","article-title":"NLG919\/cyclodextrin complexation and anti-cancer therapeutic benefit as a potential immunotherapy in combination with paclitaxel","volume":"138","author":"Xu","year":"2019","journal-title":"Eur. J. Pharm. Sci."},{"key":"nanoab824dbib14","doi-asserted-by":"publisher","first-page":"4015","DOI":"10.1200\/JCO.2018.36.15_suppl.4015","type":"journal-article","article-title":"Phase 2 trial of the IDO pathway inhibitor indoximod plus gemcitabine\/Nab-paclitaxel for the treatment of patients with metastatic pancreas cancer","volume":"36","author":"Bahary","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"nanoab824dbib15","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.v29.49","type":"journal-article","article-title":"Multiantigenic nanoformulations activate anticancer immunity depending on size","volume":"29","author":"Li","year":"2019","journal-title":"Adv. Funct. Mater."},{"key":"nanoab824dbib16","doi-asserted-by":"publisher","first-page":"5769","DOI":"10.1007\/s12274-018-2124-7","type":"journal-article","article-title":"Polymer nanoparticles as adjuvants in cancer immunotherapy","volume":"11","author":"Li","year":"2018","journal-title":"Nano Res."},{"key":"nanoab824dbib17","doi-asserted-by":"publisher","DOI":"10.1002\/advs.v6.17","type":"journal-article","article-title":"Immunomodulatory nanosystems","volume":"6","author":"Feng","year":"2019","journal-title":"Adv. Sci."},{"key":"nanoab824dbib18","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1016\/j.apsb.2018.05.005","type":"journal-article","article-title":"Human carboxylesterases: a comprehensive review","volume":"8","author":"Wang","year":"2018","journal-title":"Acta Pharm. Sin. B"},{"key":"nanoab824dbib19","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/S1046-5928(03)00218-3","type":"journal-article","article-title":"Purification of brain tubulin through two cycles of polymerization-depolymerization in a high-molarity buffer","volume":"32","author":"Castoldi","year":"2003","journal-title":"Protein Expr. Purif."},{"key":"nanoab824dbib20","doi-asserted-by":"publisher","first-page":"10242","DOI":"10.1021\/acsnano.9b03466","type":"journal-article","article-title":"High affinity of chlorin e6 to immunoglobulin G for Intraoperative fluorescence image-guided cancer photodynamic and checkpoint blockade therapy","volume":"13","author":"Xu","year":"2019","journal-title":"ACS Nano"},{"key":"nanoab824dbib21","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1080\/17460441.2019.1567487","type":"journal-article","article-title":"Failures, and future prospects of prodrugs and their clinical impact","volume":"14","author":"Najjar","year":"2019","journal-title":"Expert Opin. Drug Discov."},{"key":"nanoab824dbib22","doi-asserted-by":"publisher","first-page":"7359","DOI":"10.7150\/thno.37625","type":"journal-article","article-title":"Carboxylesterase-cleavable biotinylated nanoparticle for tumor-dual targeted imaging","volume":"9","author":"Chen","year":"2019","journal-title":"Theranostics"},{"key":"nanoab824dbib23","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1158\/1078-0432.CCR-12-1184","type":"journal-article","article-title":"Human carboxylesterase-2 hydrolyzes the prodrug of gemcitabine (Ly2334737) and confers prodrug sensitivity to cancer cells","volume":"19","author":"Pratt","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"nanoab824dbib24","doi-asserted-by":"publisher","first-page":"5290","DOI":"10.1158\/1078-0432.CCR-14-0514","type":"journal-article","article-title":"Durable therapeutic efficacy utilizing combinatorial blockade against IDO, CTLA-4, and PD-L1 in mice with brain tumors","volume":"20","author":"Wainwright","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"nanoab824dbib25","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1158\/2326-6066.CIR-16-0297","type":"journal-article","article-title":"Myeloid-derived suppressor cells","volume":"5","author":"Gabrilovich","year":"2017","journal-title":"Cancer Immunol. Res."},{"key":"nanoab824dbib26","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1016\/j.it.2016.01.004","type":"journal-article","article-title":"The nature of myeloid-derived suppressor cells in the tumor microenvironment","volume":"37","author":"Kumar","year":"2016","journal-title":"Trends Immunol."}],"container-title":["Nanotechnology"],"original-title":[],"link":[{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ab824d","content-type":"text\/html","content-version":"am","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ab824d\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ab824d\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ab824d","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ab824d","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ab824d\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ab824d\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ab824d\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ab824d\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"similarity-checking"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ab824d\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ab824d","content-type":"text\/html","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ab824d\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T13:24:49Z","timestamp":1766237089000},"score":1,"resource":{"primary":{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ab824d"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,1]]},"references-count":26,"journal-issue":{"issue":"29","published-online":{"date-parts":[[2020,5,5]]},"published-print":{"date-parts":[[2020,5,1]]}},"URL":"https:\/\/doi.org\/10.1088\/1361-6528\/ab824d","relation":{},"ISSN":["0957-4484","1361-6528"],"issn-type":[{"value":"0957-4484","type":"print"},{"value":"1361-6528","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,1]]},"assertion":[{"value":"An albumin-bound drug conjugate of paclitaxel and indoleamine-2,3-dioxygenase inhibitor for enhanced cancer chemo-immunotherapy","name":"article_title","label":"Article Title"},{"value":"Nanotechnology","name":"journal_title","label":"Journal Title"},{"value":"paper","name":"article_type","label":"Article Type"},{"value":"\u00a9 2020 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.","name":"copyright_information","label":"Copyright Information"},{"value":"2020-01-14","name":"date_received","label":"Date Received","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2020-03-23","name":"date_accepted","label":"Date Accepted","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2020-05-05","name":"date_epub","label":"Online publication date","group":{"name":"publication_dates","label":"Publication dates"}}]}}