Functionalized single-walled carbon nanotubes as rationally designed vehicles for tumor-targeted drug delivery.
Functionalized single-walled carbon nanotubes as rationally designed vehicles for tumor-targeted drug delivery.
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DOI：
10.1021/ja805570f
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发表时间：
2008-12-10
影响因子：
15
通讯作者：
Ojima, Iwao
中科院分区：
文献类型：
--
作者：
Chen, Jingyi;Chen, Shuyi;Zhao, Xianrui;Kuznetsova, Larisa V.;Wong, Stanislaus S.;Ojima, Iwao
一种新型的基于单壁碳纳米管（SWNT）的肿瘤靶向药物递送系统（DDS）被开发出来，该系统由一个功能化的碳纳米管与肿瘤靶向模块以及前药模块相连接组成。这种纳米级DDS有三个关键特征：(a)使用功能化的SWNTs作为递送治疗药物或诊断的生物相容性平台，(b)结合抗癌剂的前药模块（类taxoid与可切割连接体），在内化和原位药物释放时在肿瘤细胞内被激活为其细胞毒性形式，以及(c)将肿瘤识别模块（生物素和间隔物）附着在纳米管表面。为了证明该DDS的有效性，设计、合成了三种荧光和荧光分子探针，对其进行了表征，并利用共聚焦荧光显微镜对癌细胞（L1210FR白血病细胞系）内受体介导的内吞作用和药物释放进行了分析。我们还评估了该偶联物的特异性和细胞毒性，并将其与L1210和人类非癌细胞系进行了比较。至此，已经明确证明了这种肿瘤靶向DDS完全按照设计的方式工作，并且对特定的癌细胞系表现出高效力，从而为进一步的开发奠定了坚实的基础。
A novel single-walled carbon nanotube (SWNT)-based tumor-targeted drug delivery system (DDS) has been developed, which consists of a functionalized SWNT linked to tumor-targeting modules as well as prodrug modules. There are three key features of this nanoscale DDS: (a) use of functionalized SWNTs as a biocompatible platform for the delivery of therapeutic drugs or diagnostics, (b) conjugation of prodrug modules of an anticancer agent (taxoid with a cleavable linker) that is activated to its cytotoxic form inside the tumor cells upon internalization and in situ drug release, and (c) attachment of tumor-recognition modules (biotin and a spacer) to the nanotube surface. To prove the efficacy of this DDS, three fluorescent and fluorogenic molecular probes were designed, synthesized, characterized and subjected to the analysis of the receptor-mediated endocytosis and drug release inside the cancer cells (L1210FR leukemia cell line) by means of confocal fluorescence microscopy. The specificity and cytotoxicity of the conjugate have also been assessed and compared with L1210 and human non-cancerous cell lines. Then, it has unambiguously been proven that this tumor-targeting DDS works exactly as designed and shows high potency towards specific cancer cell lines, thereby forming a solid foundation for further development.
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DOI：
10.1073/pnas.68.10.2604
发表时间：
1971-01-01
影响因子：
11.1
作者：
BECKER, JM;WILCHEK, M;KATCHALS.E
通讯作者：
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影响因子：
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作者：
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作者：
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影响因子：
3.2
作者：
Gao, LZ;Nie, L;Yan, XY
通讯作者：
Yan, XY