N-acetylgalactosamine-functionalized dendrimers as hepatic cancer cell-targeted carriers.
N-acetylgalactosamine-functionalized dendrimers as hepatic cancer cell-targeted carriers.
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DOI：
10.1016/j.biomaterials.2010.11.068
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发表时间：
2011-06
期刊：
影响因子：
14
通讯作者：
El-Sayed, Mohamed E. H.
中科院分区：
文献类型：
--
作者：
Medina, Scott H.;Tekumalla, Venkatesh;Chevliakov, Maxim V.;Shewach, Donna S.;Ensminger, William D.;El-Sayed, Mohamed E. H.
目前迫切需要一种新型的聚合物载体，可以选择性地将大剂量的化疗药物输送到肝癌细胞中，以达到高的治疗活性和最小的全身副作用。PAMAM树状大分子具有独特的分支结构和大量适合于化疗药物偶联的化学表面基团。在这篇文章中，我们报道了n -乙酰半乳糖胺（NAcGal）通过肽和硫脲键偶联到聚氨基胺（PAMAM-NH2）树状大分子的第5代（G5），以制备NAcGal靶向载体，用于靶向递送化疗药物到肝癌细胞。我们描述了naccal靶向和非靶向G5树突状分子进入肝癌细胞（HepG2）的作用，作为G5浓度和孵育时间的函数。通过竞争性抑制实验，我们研究了asialglycoprotein receptor （ASGPR）在nacgal靶向树突状分子内化到肝癌细胞中的作用。我们的研究结果表明，通过asgpr介导的内吞作用，ngal靶向的G5树突状分子被摄取到肝癌细胞中。这些靶向载体的内化随着G5浓度和孵育时间的增加而增加，遵循受体介导的内吞作用的Michaelis-Menten动力学特征。这些结果共同表明，G5-NAcGal偶联物作为靶向载体，选择性地将化疗药物递送到肝癌细胞中。
There is an urgent need for novel polymeric carriers that can selectively deliver a large dose of chemotherapeutic agents into hepatic cancer cells to achieve high therapeutic activity with minimal systemic side effects. PAMAM dendrimers are characterized by a unique branching architecture and a large number of chemical surface groups suitable for coupling of chemotherapeutic agents. In this article, we report the coupling of N-acetylgalactosamine (NAcGal) to generation 5 (G5) of poly(amidoamine) (PAMAM-NH2) dendrimers via peptide and thiourea linkages to prepare NAcGal-targeted carriers used for targeted delivery of chemotherapeutic agents into hepatic cancer cells. We describe the uptake of NAcGal-targeted and non-targeted G5 dendrimers into hepatic cancer cells (HepG2) as a function of G5 concentration and incubation time. We examine the contribution of the asialoglycoprotein receptor (ASGPR) to the internalization of NAcGal-targeted dendrimers into hepatic cancer cells through a competitive inhibition assay. Our results show that uptake of NAcGal-targeted G5 dendrimers into hepatic cancer cells occurs via ASGPR-mediated endocytosis. Internalization of these targeted carriers increased with the increase in G5 concentration and incubation time following Michaelis–Menten kinetics characteristic of receptor-mediated endocytosis. These results collectively indicate that G5-NAcGal conjugates function as targeted carriers for selective delivery of chemotherapeutic agents into hepatic cancer cells.
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影响因子：
10.8
作者：
El-Sayed, M;Ginski, M;Ghandehari, H
通讯作者：
Ghandehari, H
影响因子：
11.2
作者：
Kukowska-Latallo, JF;Candido, KA;Baker, JR
通讯作者：
Baker, JR
影响因子：
1.7
作者：
El-Sayed, M;Ginski, M;Ghandehari, H
通讯作者：
Ghandehari, H
DOI：
10.1016/j.nano.2008.12.007
发表时间：
2009-09-01
影响因子：
5.4
作者：
Navarro, Gemma;Tros de ILarduya, Conchita
通讯作者：
Tros de ILarduya, Conchita
影响因子：
4.9
作者：
Albertazzi, Lorenzo;Serresi, Michela;Beltram, Fabio
通讯作者：
Beltram, Fabio