Programming Drug Delivery Kinetics for Active Burst Release with DNA Toehold Switches

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery Systems

Background:

• Current smart drug delivery systems (DDSs) face challenges in precise, controllable drug release within targeted tumor cells.
• Achieving high delivery efficiency and efficacy in chemotherapy remains a significant hurdle.

Purpose of the Study:

• To develop a DNA toehold switch-engineered spherical nucleic acid-templated hydrogel (SNAgel) for on-site, active burst release of chemotherapeutic drugs.
• To enable precise and controllable drug release kinetics in target cancer cells.

Main Methods:

• Engineered SNAgels using DNA toehold switches and hybridization chain reaction (HCR).
• Designed ligand-specific toehold sequences to control drug release kinetics (t1/2 from 60.52 to 5.49 min).
• Utilized a compact DNA shell for camouflage, prolonging circulation and enhancing tumor targeting.

Main Results:

• Demonstrated active burst release of chemotherapeutic payloads with tunable kinetics.
• SNAgels exhibited prolonged blood circulation, targeted accumulation, and efficient cell entry in vivo.
• Significant enhancement in anticancer activity observed in cancer cell lines and tumor-bearing mice.

Conclusions:

• The DNA-engineered kinetic control approach offers a new strategy for developing advanced DDSs.
• SNAgels show potential as a paradigm-shifting platform for cancer therapeutics.
• This method provides precise, on-demand drug release for improved cancer treatment outcomes.