期刊
BIOMATERIALS
卷 32, 期 25, 页码 5900-5905出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2011.04.058
关键词
Cationic cholesteryl group-bearing pullulans; Macropinocytosis; Lymphocyte; Nanoparticle; Hydrogel; Protein delivery
资金
- Ministry of Education, Culture, Sport, Science and Technology of Japan
- Grants-in-Aid for Scientific Research [22114009, 23790531, 23390063] Funding Source: KAKEN
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. (C) 2011 Elsevier Ltd. All rights reserved.
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