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Additionally, low penetration efficiency and unpredictable drug release in tumor areas restrict tumor therapy.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>A triblock copolymeric micelle (Nano<jats:sup>PCPT+PIMDQ<\/jats:sup>) was developed to carry the chemotherapeutic drug camptothecin (CPT) and the TLR7\/8 agonist 1-(4-(aminomethyl)benzyl)-2-butyl-1H-imidazo[4,5-c] quinoline-4-amine (IMDQ) to achieve deep tumor penetration and on-demand drug release by responding to acid and reduction stimuli sequentially. The synergistic antitumour efficacy of Nano<jats:sup>PCPT+PIMDQ<\/jats:sup> was assessed both in vitro and in vivo.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Nano<jats:sup>PCPT+PIMDQ<\/jats:sup> is composed of a hydrophilic PEG(polyethylene glycol) outer layer, an acid-sensitive EPEMA middle layer, and a drug inner core. Upon intratumoral injection, (i) Nano<jats:sup>PCPT+PIMDQ<\/jats:sup> first responds to the acidic tumor microenvironment and disintegrates to PIMDQ and PCPT, penetrating deep regions of the tumor; (ii) tumor cells are killed by the released CPT; (iii) DCs are activated by PIMDQ to increase the infiltration of cytotoxic T lymphocyte (CTL); and (iv) both downregulated Foxp3<jats:sup>+<\/jats:sup> Tregs by CPT and repolarized M2 macrophages by PIMDQ can relieve the TIME.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>This pH\/GSH-responsive triblock polymer-drug conjugate reduces immunosuppression and enhances the infiltration of CTLs by codelivering CPT and IMDQ in a controllable manner, providing a promising platform for synergistic tumor chemoimmunotherapy.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12951-022-01577-5","type":"journal-article","created":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T11:07:18Z","timestamp":1660216038000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Sequential acid\/reduction response of triblock copolymeric nanomicelles to release camptothecin and toll-like receptor 7\/8 agonist for orchestrated chemoimmunotherapy"],"prefix":"10.1186","volume":"20","author":[{"given":"Xiaoyan","family":"Ge","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanyun","family":"Hao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huajun","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yutong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xia","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongfei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Zou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiying","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingling","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gang","family":"Shan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiyue","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,8,11]]},"reference":[{"key":"1577_CR1","doi-asserted-by":"publisher","first-page":"eabc2816","DOI":"10.1126\/scitranslmed.abc2816","volume":"13","author":"L Chen","year":"2021","unstructured":"Chen L, Qin H, Zhao R, Zhao X, Lin L, Chen Y, Lin Y, Li Y, Qin Y, Li Y, et al. 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