Targeted gene delivery to sinusoidal endothelial cells: DNA nanoassociate bearing hyaluronan‐glycocalyx

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Abstract
SPECIFIC AIMSLiver sinusoidal endothelial cells (SECs) possess unique receptors that recognize and internalize hyaluronic acid (HA). We used this characteristic and the unique assembling properties of comb-type polycations with DNA to develop a system for targeting foreign DNA to SECs.PRINCIPAL FINDINGS1. Synthesis of hyaluronate-grafted poly(l-lysine) copolymerHA (Mn 3.2×105) was enzymatically digested by hyaluronidase to obtain low molecular weight fragments. The HA fragments (Mn 1.5×104) were conjugated to poly(l-lysine) (PLL) by a reductive amination reaction using sodium cyanoborohydride (NaBH3CN) as a reductant. The resulting comb-type copolymer (hyaluronate-grafted poly(l-lysine), PLL-g-HA) was isolated from unreacted HA fragments by dialyzing against 1 M NaCl through membranes with a molecular weight limit of 25,000 and lyophilized. Copolymer composition was determined from 1H-NMR spectra in D2O containing 500 mM NaCl.2. Formation of the PLL-g-HA/DNA complexPLL-g-HA was mixed with DNA in 154 mM Na...