In situ forming oxygen/ROS-responsive niche-like hydrogel enabling gelation-triggered chemotherapy and inhibition of metastasis.
In situ forming oxygen/ROS-responsive niche-like hydrogel enabling gelation-triggered chemotherapy and inhibition of metastasis.
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DOI：
10.1016/j.bioactmat.2022.08.002
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发表时间：
2023-03
影响因子：
18.9
通讯作者：
Chen, Hangrong
中科院分区：
文献类型：
--
作者：
Chen, Shi-Xiong;Zhang, Ji;Xue, Fengfeng;Liu, Wei;Kuang, Yichen;Gu, Bingxin;Song, Shaoli;Chen, Hangrong
尽管在过去的几十年里，各种低氧激活的前药（HAP）的开发取得了很大进展，但目前基于HAP的癌症治疗仍然存在许多障碍，例如，缺氧区难以深入治疗效果差，缺氧易发生转移。受工程生态位的启发，合成了一种新型的功能性壳聚糖聚合物（CS-FTP），用于构建基于水凝胶的生物生态位（CS-FTP-gel），旨在重塑肿瘤缺氧微环境。CS-FTP聚合物在注射到肿瘤中后通过酶介导的耗氧二聚化交联以形成壁龛样水凝胶，其中HAP（即，AQ 4 N）可以物理包封，导致增强的肿瘤缺氧，以促进AQ 4 N-AQ 4毒性转化，从而使化疗的功效最大化。此外，帕唑帕尼（PAZ）通过ROS敏感性连接体缀合到CS骨架上，经历刺激响应性释放行为，以促进肿瘤饥饿的抗血管生成，最终有助于抑制肺转移，并与基于AQ 4 N的化疗协同作用于原位4 T1乳腺肿瘤模型。本研究为低氧化疗提供了一个有前途的策略，并证明了多功能水凝胶适用于抗肿瘤治疗的令人鼓舞的临床潜力。CS-FTP显示酶介导的缺氧诱导的凝胶化和活性氧（ROS）响应的药物释放。肿瘤内形成的CS-FTP凝胶可用作生物小生境以增强肿瘤缺氧微环境。体内PET/CT直接监测肿瘤缺氧变化，证实CS-FTP增强肿瘤缺氧的能力。ROS响应性CS-FTP的耗氧凝胶化触发用于抗转移的化学疗法和饥饿疗法。
Though the development of the diverse hypoxia-activated prodrugs (HAPs) has made great progresses in the last several decades, current cancer therapy based on HAPs still suffers many obstacles, e.g., poor therapeutic outcome owing to hard deep reaching to hypoxic region, and the occurrence of metastasis due to hypoxia. Inspired by engineered niches, a novel functional chitosan polymer (CS-FTP) is synthesized for construction of a hydrogel-based bio-niche (CS-FTP-gel) in aiming at remodeling tumor hypoxic microenvironment. The CS-FTP polymers are crosslinked to form a niche-like hydrogel via enzyme-mediated oxygen-consumable dimerization after injected into tumor, in which a HAP (i.e., AQ4N) could be physically encapsulated, resulting in enhanced tumor hypoxia to facilitate AQ4N-AQ4 toxic transformation for maximizing efficacy of chemotherapy. Furthermore, Pazopanib (PAZ) conjugated onto the CS backbone via ROS-sensitive linker undergoes a stimuli-responsive release behavior to promote antiangiogenesis for tumor starvation, eventually contributing to the inhibition of lung metastasis and synergistic action with AQ4N-based chemotherapy for an orthotopic 4T1 breast tumor model. This study provides a promising strategy for hypoxia-based chemotherapy and demonstrates an encouraging clinical potential for multifunctional hydrogel applicable for antitumor treatment. CS-FTP shows enzyme-mediated hypoxia-inducible gelation and reactive oxygen species (ROS)-responsive drug release. CS-FTP gel formed intratumorally can be used as a bio-niche to enhance tumor hypoxic microenvironment. In vivo PET/CT directly monitors the tumor hypoxia changes and confirm the ability of CS-FTP to enhance tumor hypoxia. Oxygen-consumable gelation of ROS-responsive CS-FTP triggers chemotherapy and starvation therapy for antimetastasis.
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影响因子：
19
作者：
Li, Zhenhua;Zhu, Dashuai;Wang, Xiaojie
通讯作者：
Wang, Xiaojie
影响因子：
10.8
作者：
Li, Shanshan;Xie, Aiqing;Zhang, Qixiong
通讯作者：
Zhang, Qixiong
骨靶向的红细胞癌杂种杂交膜膜纳米颗粒，以增强OSCC对骨侵袭的光热和缺氧的化学疗法。
影响因子：
10.2
作者：
Chen H;Deng J;Yao X;He Y;Li H;Jian Z;Tang Y;Zhang X;Zhang J;Dai H
通讯作者：
Dai H
影响因子：
30.8
作者：
Bhandari, Vinayak;Hoey, Christianne;Bristow, Robert G.
通讯作者：
Bristow, Robert G.
2-巯基苯并噻唑在黄铜矿和闪锌矿表面的吸附机理：从头算和光谱研究
DOI：
10.1016/s1003-6326(15)63854-7
发表时间：
2015-07-01
影响因子：
4.5
作者：
Jiao, Fen;Qin, Wen-qing;Wang, Xing-jie
通讯作者：
Wang, Xing-jie