材料科学
药品
药物输送
肿瘤微环境
癌症研究
药理学
纳米技术
医学
肿瘤细胞
作者
Yajun Xu,Jianlin Lv,Fuyao Liu,Jinqiang Wang,Liu Ya,Chaoying Kong,Yanran Li,Na Shen,Zhen Gu,Zhaohui Tang,Xuesi Chen
标识
DOI:10.1002/adma.202312493
摘要
Abstract Toll‐like receptor 7/8 agonists, such as imidazoquinolines (IMDQs), are promising for the de novo priming of antitumor immunity. However, their systemic administration is severely limited due to the off‐target toxicity. Here, we describe a sequential drug delivery strategy. The formulation is composed of two sequential modules: a tumor microenvironment remodeling nanocarrier (poly( L ‐glutamic acid)‐ graft‐ methoxy poly(ethylene glycol)/combretastatin A4, termed CA4‐NPs) and an immunotherapy nanocarrier (apcitide peptide‐decorated poly( L ‐glutamic acid)‐ graft ‐IMDQ‐N 3 conjugate, termed apcitide‐PLG‐IMDQ‐N 3 ). CA4‐NPs, as a vascular disrupting agent, are utilized to remodel the tumor microenvironment for enhancing tumor coagulation and hypoxia. Subsequently, the apcitide‐PLG‐IMDQ‐N 3 could identify and target tumor coagulation through the binding of surface apcitide peptide to the GPIIb‐IIIa on activated platelets. Afterward, IMDQ was activated selectively through the conversion of “‐N 3 ” to “‐NH 2 ” in the presence of hypoxia. The biodistribution results confirmed their high tumor uptake of activated IMDQ (22.66%ID/g). By augmenting the priming and immunologic memory of tumor‐specific CD8 + T cells, 4T1 and CT26 tumors with a size of ∼500 mm 3 were eradicated without recurrence in mouse models. This article is protected by copyright. All rights reserved
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