[Frontiers in Bioscience 16, 2970-2987, June 1, 2011]

[Frontiers in Bioscience 16, 2970-2987, June 1, 2011]

Glycosylated carriers for cell-selective and nuclear delivery of nucleic acids

Wassana Wijagkanalan^1,2,3, Shigeru Kawakami¹, Mitsuru Hashida^1,3

1Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan, ²The Japan Society for the Promotion of Science (JSPS), Chiyoda-ku, Tokyo 102-8471, Japan, ³Institute of Integrated Cell-Material Sciences (iCeMS), Kyoto University, Kyoto 606-8501, Japan

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Non-targeted delivery of nucleic acids
4. The rationale of glycosylation for targeted delivery of nucleic acids
5. Glycosylated carriers for cell-selective delivery of nucleic acids: 5.1. Hepatocytes; 5.2. Macrophages; 5.3. Dendritic cells; 5.4. Hepatic stellate cells; 5.5. Lung epithelial cells; 5.6. Inflamed or activated endothelial cells; 5.7. Cancer cells
6. Glycosylated carriers for endosomal escape and nuclear delivery of nucleic acids
7. Factors affecting targeted delivery of nucleic acids using glycosylated carries: 7.1. Size; 7.2. Surface potential; 7.3. State of target cells
8. Perspectives
9. Concluding remarks
10. Acknowledgment
11. References

1. ABSTRACT

Targeted gene delivery via selective cellular receptors has been realized as a crucial strategy for successful gene therapy by maximizing therapeutic efficiency in target cells and minimizing systemic toxicity. The membrane carbohydrate-binding proteins (membrane lectins) with different carbohydrate specificities are differentially expressed on the cellular and intracellular membranes of a number of cells. Their multiplicity, high affinity, and effective endocytosis after receptor binding as well as the biocompatibility of carbohydrate ligands endow them as potential ligands for glycosylated carriers in cell-selective delivery of nucleic acids. To achieve the in vivo application, glycosylated carriers/nucleic acid complexes have to fulfill certain conditions, including having a suitable size, minimal nonspecific interactions, low immunogenicity, and high uptake in target cells. Accordingly, the effective nuclear delivery of nucleic acids is the paramount important step for efficient gene transfer. This review summarizes the recent progress regarding application of glycosylated carriers for cell-selective and nuclear delivery of nucleic acids and their critical factors for efficient gene transfer. In addition, the development of new materials, such as carbon nanotubes, carbon nanospheres, and gold nanoparticles, as innovative carriers will be discussed with regards to glycosylation-mediated delivery of nucleic acids.