Modulation of hydrogel nanoparticle intracellular trafficking by multivalent surface engineering with tumor targeting peptide.
Modulation of hydrogel nanoparticle intracellular trafficking by multivalent surface engineering with tumor targeting peptide.
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DOI：
10.1039/c3nr00908d
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发表时间：
2013-11-07
期刊：
影响因子：
6.7
通讯作者：
Kopelman R
中科院分区：
文献类型：
--
作者：
Karamchand L;Kim G;Wang S;Hah HJ;Ray A;Jiddou R;Koo Lee YE;Philbert MA;Kopelman R
具有肿瘤靶向配体F3肽的水凝胶纳米颗粒（NP）的表面工程化增强了NP对过表达核仁素的肿瘤细胞的结合亲和力和内化。值得注意的是，在内化后，在肿瘤细胞中，F3官能化的NP一致地表现出比非官能化的NP显著更低的向降解性溶酶体的运输。这归因于非官能化的NP，而不是F3官能化的NP，与来自肿瘤细胞表面的溶酶体相关膜蛋白-1（LAMP 1）共内化。此外，它表明，F3功能化的NP的细胞内运输显着不同于单一的F3肽。这对于设计有效的，化学响应的，控制释放的和多功能的纳米药物用于多药耐药癌症具有重要意义。
Surface engineering of a hydrogel nanoparticle (NP) with the tumor-targeting ligand, F3 peptide, enhances both the NP’s binding affinity for, and internalization by, nucleolin overexpressing tumor cells. Remarkably, the F3-functionalized NPs consistently exhibited significantly lower trafficking to the degradative lysosomes than the non-functionalized NPs, in the tumor cells, after internalization. This is attributed to the non-functionalized NPs, but not the F3-functionalized NPs, being co-internalized with Lysosome-associated Membrane Protein-1 (LAMP1) from the surface of the tumor cells. Furthermore, it is shown that the intracellular trafficking of the F3-functionalized NPs differs significantly from that of the single F3 peptides. This has important implications for designing effective, chemically-responsive, controlled-release and multifunctional nanodrugs for multi-drug-resistant cancers.
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作者：
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