A Complementary Strategy for Enhancement of Nanoparticle Intracellular Uptake
A Complementary Strategy for Enhancement of Nanoparticle Intracellular Uptake
复制标题
增强纳米颗粒细胞内摄取的补充策略
DOI：
10.1007/s11095-014-1307-5
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发表时间：
2014-02
影响因子：
3.7
通讯作者：
Wang, Ying
中科院分区：
文献类型：
--
作者：
Zhong, Lijuan;Cai, Hongbing;Zhang, Xingmei;Wang, Ying
目的将靶向配体介导的选择性和CPP介导的跨膜功能相结合的互补策略可协同增强带负电荷纳米颗粒的细胞摄取。采用互补策略制备了一种带负电荷的肝素纳米粒，以期在高效摄取紫杉醇的同时，发挥更强的抗癌活性。MethodsWe合成了一种以叶酸为靶向配体、以磷酸肽达特为配体的肝素纳米粒（H-F-Tat-P NPs）。用1H NMR、DLS和TEM对纳米粒子进行了表征。研究了双配体对体系在水溶液中行为的影响。此外，通过流式细胞仪、共聚焦显微镜和MTT法检测其细胞内化和抗癌活性。ResultsFolate在肝素基纳米粒的形成中起关键作用，依赖于两亲性达特和疏水性叶酸的平衡。虽然H-F-Tat-P NP主要通过相似的途径进入FR特异性和非特异性细胞，但由于细胞类型特异性变化，没有可比性。与非特异性细胞不同，互补配体可以帮助带负电荷的NPs增强细胞摄取，促进其在特定细胞中的内体逃逸，从而表现出很大的抗癌活性。
PurposeThe complementary strategy by combining targeting ligand-mediated selectivity and CPP-mediated transmembrane function could be exploit synergies for enhancing cellular uptake of nanoparticles with negative charge. A heparin-based nanoparticles with negative charge was fabricated by complementary strategy, which was expected to attain efficient uptake and simultaneously exert great anticancer activity.MethodsWe synthesized heparin-based nanoparticles with targeting ligand folate and CPP ligand Tat to deliver paclitaxel (H-F-Tat-P NPs). The NPs were characterized by1H NMR, DLS and TEM, respectively. The effect of dual ligands on system behavior in aqueous solution was investigated. Moreover, its cellular internalization and anticancer activity were detected by flow cytometry, confocal microscopy and MTT.ResultsFolate played a key role in the formation of heparin-based NPs dependent on the balance of amphiphilic Tat and hydrophobic folate. Although H-F-Tat-P NPs primarily entered FR specific and non-specific cells by similar routes, there were no comparability due to cell-type specific variation. Unlike non-specific cells, the complementary ligands could help negative-charged NPs to enhance cellular uptake facilitating its endosome escape in specific cells thereby exhibiting great anticancer activity.ConclusionsThe complementary strategy for negative-charged NPs was presented a promising delivery system for diverse anticancer agents enable simultaneously targeting and drug delivery.
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影响因子：
3.4
作者：
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通讯作者：
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影响因子：
9.7
作者：
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通讯作者：
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影响因子：
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影响因子：
14
作者：
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通讯作者：
Tang, Gu-Ping
影响因子：
11.2
作者：
T. Tran;Byoung-chan Bae;Yong-kyu Lee;K. Na;K. Huh
通讯作者：
T. Tran;Byoung-chan Bae;Yong-kyu Lee;K. Na;K. Huh