Assembly of ionic supramolecular polymers using a decacationic pillar[5]arene to noncovalently crosslink hyaluronic acid for short DNA delivery

Abstract

Three ionic supramolecular polymers (ISPs) have been assembled from an imidazolium-modified decacationic pillar[5]arene (P5A) and hyaluronic acid (HA, MW = 3000 Da) by controlling their molar ratio at 1 : 0.2, 1 : 0.4 or 1 : 0.6. Dynamic light scattering experiments show that at [P5A] = 16 μM the ISPs afford nano-scale aggregates with hydrodynamic diameters of 21, 33 and 21 nm, respectively. Fluorescence and zeta potential experiments support that the ISPs include short single- and double-stranded DNA of 21 nucleotides. Fluorescence imaging and flow cytometric analysis demonstrate that the ISPs can deliver the included DNA into both normal and cancer cells, with the percentage of delivered cells reaching up to 99.7%. In vitro and in vivo assays reveal that the second ISP has the highest biocompatibility, and mixing with HA improves the biocompatibility of P5A.