Hyaluronic acid and its derivative as a multi-functional gene expression enhancer: Protection from non-specific interactions, adhesion to targeted cells, and transcriptional activation

Abstract

Hyaluronic acid (HA), a natural anionic mucopolysaccharide, can be deposited onto the cationic surface of DNA/polyethyleneimine (PEI) complexes to recharge the surface potential and reduce nonspecific interactions with proteins. HA can also be used as a ligand to target specific cell receptors. Furthermore, HA-coating enhanced the transcriptional activity of the plasmid/PEI complexes, probably by loosening the tight binding between DNA and PEI, which facilitated the approach of transcription factors. Amphoteric HA derivative having spermine side chains (Spn-HA) with a structure similar to HMG protein showed higher transcription-enhancing activity than HA. Plasmid/PEI/Spn-HA ternary complex exhibited 29-fold higher transgene expression efficiency than naked plasmid/PEI complexes in CHO cells.

Bioadhesive hyaluronan–chitosan nanoparticles can transport genes across the ocular mucosa and transfect ocular tissue

“…31,32 In addition, the positive effect of HA could be understood by its known capacity of being able to enter the cell nucleus 33,34 and also to its suggested role as a transcription activator. 35 Similar results in terms of transfection efficiency have been previously observed for the same nanoparticles in HCE proliferating cells. …”

Polysaccharide-Based Nanoparticles for Controlled Release Formulations

“…Like other glycosaminoglycans, hyaluronan can serve as a targeting vehicle for the delivery of chemotherapeutic agents to cancerous tissues, as many tumours over express the hyaluronan CD44 and RHAMM receptors (Yip et al, 2006). As a drug delivery carrier, HA has several advantages including the negligible non-especific interaction with serum components due to its polyanionic characteristics (Ito et al, 2006) and the highly efficient targeted specific delivery to the liver tissues with HA receptors (Zhou et al, 2003).…”

A comparative study of three ternary complexes prepared in different mixing orders of siRNA/redox-responsive hyperbranched poly (amido amine)/hyaluronic acid

“…35,38 FAM-siRNA/PCD/HA ternary complexes (P/N/C charge ratio = 1/20/16) were prepared by different mixing orders using the same siRNA concentration. Then, relative fluorescence intensity of FAM-siRNA in each ternary complex was determined using a spectrofluorophotometer (Cary-Eclipse; Varian Medical Systems, Inc, Palo Alto, CA) at an excitation wavelength of 480 nm and an emission wavelength of 520 nm.…”

“…[30][31][32][33] Recent studies have demonstrated that HA-coated electrostatic complexes display a great number of attractive properties, including preparation of very small vesicles, 34 better transfection efficacy, 25 and better target specificity. 35 In this study, the authors synthesized a type of redoxresponsive hyperbranched poly(amido amine)s (named PCD) to form siRNA/PCD/HA ternary complexes with three different mixing orders ( Figure 1B). As these ternary complexes form spontaneously upon mixing, the authors hypothesized that different mixing orders result in different assembly structures, which may affect the siRNA delivery efficiency.…”