Highly effective gene delivery based on cyclodextrin multivalent assembly in target cancer cells

Abstract

Nucleic acid condensation and controlled release remain significant challenges of gene therapy in the fields of chemical biology and nanotechnology. In this work, we have reported a polysaccharide supramolecular assembly constructed using upconversion nanoparticles encapsulated by β-cyclodextrin-grafted hyaluronic acid (HACD-UCNPs) and spermine modified with arylazopyrazoles (AAPS). Through UV-Vis spectroscopy, transmission electron microscopy (TEM), dynamic light scattering (DLS), gel electrophoresis, confocal laser imaging and combination experiments, such an assembly can achieve not only nucleic acid condensation but also targeted cells delivery and controlled release. Furthermore, we investigated the ability of the system to deliver siRNA under hypoxic conditions, and the subsequent NIR irradiation regulation achieved the two-step release of RNA, obtaining the best effect. This strategy provides a new approach for nucleic acid condensation and targeted delivery, which may bring broad potential in gene therapy.