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DNA-Scaffolded Disulfide Redox Network for Programming Drug-Delivery Kinetics
Wei Ji1, Xiaodan Li1, Mingshu Xiao1
1Department Shanghai Key Laboratory of Green Chemistry and Chemical Processes School of Chemistry and Molecular Engineering, East China Normal University, 500 Dongchuan Road, Shanghai, 200241, P. R. China.
Chemistry (Weinheim an Der Bergstrasse, Germany)
|March 29, 2021
Summary
Researchers developed a DNA-scaffolded disulfide redox network (DdiSRN) for precise control over drug delivery kinetics. This innovative material enhances cancer treatment by enabling tunable, stimuli-responsive cargo release within therapeutic windows.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Chemical Biology
Background:
- Dynamic covalent materials offer potential for controlled drug release via reversible bond formation.
- Programming drug-delivery kinetics using dynamic covalent chemistry presents significant challenges.
Purpose of the Study:
- To develop a novel DNA-scaffolded disulfide redox network (DdiSRN) for precise control over drug delivery kinetics.
- To demonstrate the ability to tune drug release rates for enhanced cancer therapy.
Main Methods:
- In situ polymerization to create a DNA-scaffolded disulfide redox network (DdiSRN).
- Utilizing nucleic acids as scaffolds for dynamic disulfide bonds.
- Tuning disulfide bond density by controlling position and number on DNA scaffolds.
Main Results:
- The DdiSRN enables selective cargo release inside cancer cells in response to redox stimuli.
- Drug-delivery kinetics were programmable, with half-life decreasing from 8.3 to 4.4 hours.
- In vitro and in vivo studies showed enhanced therapeutic effects for multidrug-resistant cancer via co-delivery of DOX and siRNA.
Conclusions:
- The DdiSRN platform provides precise kinetic control over drug delivery.
- This approach enhances therapeutic efficacy for multidrug-resistant cancers.
- The DdiSRN represents a promising paradigm for precision cancer medicine.
