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

Area of Science:

• Chemical Biology
• Nanotechnology
• Biomaterials Science

Background:

• Nucleic acid condensation and controlled release are critical challenges in gene therapy.
• Existing methods often lack efficiency in targeted delivery and precise release mechanisms.

Purpose of the Study:

• To develop a polysaccharide supramolecular assembly for efficient nucleic acid condensation and controlled release.
• To investigate targeted cell delivery and RNA release under specific conditions, particularly hypoxia.
• To explore the potential of this system for advanced gene therapy applications.

Main Methods:

• Construction of a supramolecular assembly using upconversion nanoparticles (UCNPs) encapsulated by β-cyclodextrin-grafted hyaluronic acid (HACD-UCNPs) and spermine modified with arylazopyrazoles (AAPS).
• Characterization using UV-Vis spectroscopy, transmission electron microscopy (TEM), dynamic light scattering (DLS), and gel electrophoresis.
• Evaluation of cellular delivery and RNA release via confocal laser imaging and combination experiments, including hypoxic conditions and near-infrared (NIR) irradiation.

Main Results:

• The HACD-UCNP and AAPS assembly successfully achieved nucleic acid condensation.
• The system demonstrated targeted cell delivery and controlled release of nucleic acids.
• Effective siRNA delivery under hypoxic conditions was observed, with NIR irradiation enabling a two-step RNA release for optimal therapeutic outcomes.

Conclusions:

• The developed polysaccharide supramolecular assembly offers a novel strategy for nucleic acid condensation and targeted delivery.
• This approach shows significant potential for overcoming current gene therapy limitations.
• The system's ability to achieve controlled, stimuli-responsive RNA release broadens its applicability in gene therapy.