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The use of cationic nanogels to deliver proteins to myeloma cells and primary T lymphocytes that poorly express heparan sulfate

Paper ID Volume ID Publish Year Pages File Format Full-Text
7925 569 2011 6 PDF Available
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.

Keywords
Cationic cholesteryl group-bearing pullulans; Macropinocytosis; Lymphocyte; Nanoparticle; Hydrogel; Protein delivery
First Page Preview
The use of cationic nanogels to deliver proteins to myeloma cells and primary T lymphocytes that poorly express heparan sulfate
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 32, Issue 25, September 2011, Pages 5900–5905
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering