叶黄素
奥沙利铂
吉西他滨
胰腺癌
伊立替康
紫杉醇
药理学
医学
癌症研究
联合疗法
药品
药物输送
化疗
癌症
材料科学
肿瘤科
内科学
结直肠癌
纳米技术
作者
Xiaomin Jiang,Morten J. Lee,Taokun Luo,Langston Tillman,Wenbin Lin
出处
期刊:Biomaterials
[Elsevier]
日期:2023-10-01
卷期号:301: 122235-122235
被引量:3
标识
DOI:10.1016/j.biomaterials.2023.122235
摘要
The combination chemotherapy regimen FOLFIRINOX comprising folinic acid, 5-fluorouracil, irinotecan, and oxaliplatin is the first-line treatment for patients with advanced pancreatic cancer, but its use remains prohibitive for the majority of patients due to severe side effects. Here, we report a core-shell nanoscale coordination polymer (NCP) nanoparticle co-delivering a potent and synergistic combination of oxaliplatin, gemcitabine, and SN38 (OGS), for the treatment of pancreatic cancer in mouse models. OGS contains key synergistic components of FOLFIRINOX in a controllable drug ratio., It exhibited particle stability in blood circulation and enhanced deposition of the drugs in acidic tumor environments. In vitro, OGS showed superior cytotoxicity over free drug combinations and robust cytotoxic synergism among its three components. In vivo, OGS improved drug circulation, increased tumor deposition, and exhibited superior antitumor efficacy over the free drug combination in both subcutaneous and orthotopic pancreatic tumor models. OGS treatment achieved 75–91% tumor growth inhibition and prolonged mouse survival by 1.6- to 2.8-folds while minimizing systemic toxicities such as neutropenia, hepatotoxicity, and renal toxicity. This work uncovers a novel and clinically relevant nanomedicine strategy to co-deliver synergistic combination chemotherapies for difficult-to-treat cancers.
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