title: The use of cationic nanogels to deliver proteins to myeloma cells and primary T lymphocytes that poorly express heparan sulfate.
abstract: 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.
authors: Laboratory of Immunology, Graduate School of Biomedical Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors: Kozo
authors: K
authors: Watanabe
authors: Yumiko
authors: Y
authors: Tsuchiya
authors: Yoshinori
authors: Y
authors: Kawaguchi
authors: Shin-ichi
authors: S
authors: Sawada
authors: Hirohito
authors: H
authors: Ayame
authors: Kazunari
authors: K
authors: Akiyoshi
authors: Takeshi
authors: T
authors: Tsubata