Validation of a dual role of methotrexate-based chitosan nanoparticles in vivo
Validation of a dual role of methotrexate-based chitosan nanoparticles in vivo
复制标题
基于甲氨蝶呤的壳聚糖纳米粒子体内双重作用的验证
DOI：
10.1039/c5ra03705k
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发表时间：
2015-05
期刊：
影响因子：
3.9
通讯作者：
Luo Fanghong
中科院分区：
文献类型：
--
作者：
Hou Zhenqing;Lin Jinyan;Li Yanxiu;Guo Fuqiang;Yu Fei;Wu Hongjie;Fan Zhongxiong;Zhi Lili;Luo Fanghong
具有双重作用的化合物有可能将其双重功能整合到单个纳米级药物输送系统中。在这里，基于甲氨蝶呤（MTX）的聚乙二醇化壳聚糖（CS）纳米颗粒，我们在体内验证了这种双重作用，并探索了MTX作为早期肿瘤靶向配体和晚期抗癌药物的体内效率。静脉注射后，与(FA + PEG)–CS–NPs和PEG–CS–NPs相比，(MTX + PEG)–CS–NPs表现出更慢的血液清除率、更长的体循环时间和显着更大的肿瘤积累。此外，借助叶酸（FA）受体介导的内吞作用（能够在正常细胞中“关闭”细胞摄取，而在癌细胞中“开启”）和pH/细胞内蛋白酶介导的水解肽键（能够在体循环中“关闭”药物释放，而在胞内/溶酶体内“开启”），与市售的MTX相比，(MTX + PEG)–CS–NPs表现出显着优越的治疗效率。更重要的是，这项工作将激发人们对使用临床上有用的 MTX 作为协同自靶向治疗剂的兴趣，设计高度收敛、灵活和简化的纳米级药物递送系统，用于同时靶向和治疗 FA 受体过度表达的肿瘤。
A compound with a dual role has the potential to integrate its dual functions into a single nanoscale drug delivery system. Here, based on the methotrexate (MTX)-based PEGylated chitosan (CS) nanoparticles, we validated this dual role in vivo and explored the in vivo efficiency of MTX as an early-phase tumor-targeting ligand and also as a late-phase anticancer drug. Following intravenous administration, compared with the (FA + PEG)–CS–NPs and PEG–CS–NPs, the (MTX + PEG)–CS–NPs exhibited a slower blood clearance profile, longer systemic circulation time, and significantly greater tumor accumulation. Furthermore, with the aide of folate (FA) receptor-mediated endocytosis (ability to turn cellular uptake “off” in normal cells, whereas it is “on” in cancer cells) and pH/intracellular protease-mediated hydrolyzing peptide bonds (able to turn drug release “off” in systemic circulation whereas it is “on” inside endo/lysosomes), the (MTX + PEG)–CS–NPs showed remarkably superior therapeutic efficiency compared to the commercially available MTX. More importantly, this work would stimulate interest in the use of the clinically useful MTX as a synergistically self-targeted therapeutic agent in the design of a highly convergent, flexible and simplified nanoscale drug delivery system for simultaneously targeting and treating FA receptor-overexpressing tumors.
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影响因子：
4.9
作者：
Li, Yang;Wu, Hongjie;Hou, Zhenqing
通讯作者：
Hou, Zhenqing
影响因子：
4.9
作者：
van Dongen MA;Rattan R;Silpe J;Dougherty C;Michmerhuizen NL;Van Winkle M;Huang B;Choi SK;Sinniah K;Orr BG;Banaszak Holl MM
通讯作者：
Banaszak Holl MM
影响因子：
17.1
作者：
Zhang, Liangfang;Chan, Juliana M.;Gu, Frank X.;Rhee, June-Wha;Wang, Andrew Z.;Radovic-Moreno, Aleksandar F.;Alexis, Frank;Langer, Robert;Farokhzad, Omid C.
通讯作者：
Farokhzad, Omid C.
影响因子：
16.6
作者：
Li, Yuanpei;Xiao, Wenwu;Xiao, Kai;Berti, Lorenzo;Luo, Juntao;Tseng, Harry P.;Fung, Gabriel;Lam, Kit S.
通讯作者：
Lam, Kit S.
影响因子：
38.3
作者：
Jiang, Wen;Kim, Betty Y. S.;Chan, Warren C. W.
通讯作者：
Chan, Warren C. W.