The use of cationic nanogels to deliver proteins to myeloma cells and primary T lymphocytes that poorly express heparan sulfate.
The use of cationic nanogels to deliver proteins to myeloma cells and primary T lymphocytes that poorly express heparan sulfate.
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DOI：
10.1016/j.biomaterials.2011.04.058
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发表时间：
2011-09
期刊：
影响因子：
14
通讯作者：
Kozo Watanabe;Yumiko Tsuchiya;Y. Kawaguchi;S. Sawada;Hirohito Ayame;K. Akiyoshi;T. Tsubata
中科院分区：
文献类型：
--
作者：
Kozo Watanabe;Yumiko Tsuchiya;Y. Kawaguchi;S. Sawada;Hirohito Ayame;K. Akiyoshi;T. Tsubata
包含蛋白转导结构域（PTD）的融合蛋白被广泛用于外源蛋白的细胞内递送。ppd介导的递送需要在靶细胞表面表达硫酸肝素。然而，一些转移性肿瘤细胞和原发性淋巴细胞表达硫酸肝素较差。在这里，我们证明了蛋白质与阳离子含胆固醇基团的葡聚糖（cCHP）形成的纳米级水凝胶复合物可能通过诱导巨噬细胞作用有效地递送到骨髓瘤细胞和原发性CD4+T淋巴细胞，尽管由于硫酸肝素表达不良，这些细胞对ppd介导的蛋白质递送具有抗性。cCHP纳米凝胶传递的抗凋亡蛋白Bcl-xL有效阻断了这些细胞的凋亡，建立了cCHP纳米凝胶传递蛋白对细胞的功能调控。因此，cCHP纳米凝胶是一种有用的工具，可以为开发新的癌症治疗和免疫调节提供蛋白质。
Fusion proteins containing protein transduction domain (PTD) are widely used for intracellular delivery of exogenous proteins. PTD-mediated delivery requires expression of heparan sulfate on the surface of the target cells. However, some of metastatic tumor cells and primary lymphocytes poorly express heparan sulfate. Here we demonstrate that proteins complexed with nanosize hydrogels formed by cationic cholesteryl group-bearing pullulans (cCHP) are efficiently delivered to myeloma cells and primary CD4+T lymphocytes probably by induction of macropinocytosis, although these cells are resistant to PTD-mediated protein delivery as a consequence of poor heparan sulfate expression. The anti-apoptotic protein Bcl-xL delivered by cCHP nanogels efficiently blocked apoptosis of these cells, establishing functional regulation of cells by proteins delivered by cCHP nanogels. Thus, cCHP nanogel is a useful tool to deliver proteins for development of new cancer therapy and immune regulation.