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聚合物化学影响单核细胞对聚酸酐纳米球的摄取。

Polymer chemistry influences monocytic uptake of polyanhydride nanospheres.

作者信息

Ulery Bret D, Phanse Yashdeep, Sinha Avanti, Wannemuehler Michael J, Narasimhan Balaji, Bellaire Bryan H

机构信息

Department of Chemical and Biological Engineering, Iowa State University, Ames, IOWA, 50011, USA.

出版信息

Pharm Res. 2009 Mar;26(3):683-90. doi: 10.1007/s11095-008-9760-7. Epub 2008 Nov 6.

Abstract

PURPOSE

To demonstrate that polyanhydride copolymer chemistry affects the uptake and intracellular compartmentalization of nanospheres by THP-1 human monocytic cells.

METHODS

Polyanhydride nanospheres were prepared by an anti-solvent nanoprecipitation technique. Morphology and particle diameter were confirmed via scanning election microscopy and quasi-elastic light scattering, respectively. The effects of varying polymer chemistry on nanosphere and fluorescently labeled protein uptake by THP-1 cells were monitored by laser scanning confocal microscopy.

RESULTS

Polyanhydride nanoparticles composed of poly(sebacic anhydride) (SA), and 20:80 and 50:50 copolymers of 1,6-bis-(p-carboxyphenoxy)hexane (CPH) anhydride and SA were fabricated with similar spherical morphology and particle diameter (200 to 800 nm). Exposure of the nanospheres to THP-1 monocytes showed that poly(SA) and 20:80 CPH:SA nanospheres were readily internalized whereas 50:50 CPH:SA nanospheres had limited uptake. The chemistries also differentially enhanced the uptake of a red fluorescent protein-labeled antigen.

CONCLUSIONS

Nanosphere and antigen uptake by monocytes can be directly correlated to the chemistry of the nanosphere. These results demonstrate the importance of choosing polyanhydride chemistries that facilitate enhanced interactions with antigen presenting cells that are necessary in the initiation of efficacious immune responses.

摘要

目的

证明聚酐共聚物化学性质会影响THP-1人单核细胞对纳米球的摄取及细胞内区室化。

方法

通过反溶剂纳米沉淀技术制备聚酐纳米球。分别通过扫描电子显微镜和准弹性光散射确认其形态和粒径。通过激光扫描共聚焦显微镜监测不同聚合物化学性质对THP-1细胞摄取纳米球和荧光标记蛋白的影响。

结果

制备了由聚(癸二酸酐)(SA)以及1,6-双-(对羧基苯氧基)己烷(CPH)酐与SA的20:80和50:50共聚物组成的聚酐纳米颗粒,它们具有相似的球形形态和粒径(200至800nm)。纳米球与THP-1单核细胞接触后显示,聚(SA)和20:80 CPH:SA纳米球易于被内化,而50:50 CPH:SA纳米球的摄取有限。这些化学性质还不同程度地增强了红色荧光蛋白标记抗原的摄取。

结论

单核细胞对纳米球和抗原的摄取可直接与纳米球的化学性质相关。这些结果证明了选择有助于增强与抗原呈递细胞相互作用的聚酐化学性质的重要性,而这种相互作用在启动有效的免疫反应中是必需的。

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