Rational Design of DNA Framework-Based Hybrid Nanomaterials for Anticancer Drug Delivery.
Congshan WangYingjie YuMuhammad IrfanBolong XuJunjie LiLinghao ZhangZhaohui QinChangyuan YuHuiyu LiuXin SuPublished in: Small (Weinheim an der Bergstrasse, Germany) (2020)
Engineered DNA frameworks have been extensively exploited as affinity scaffolds for drug delivery. However, few studies focus on the rational design to comprehensively improve their stability, internalization kinetics, and drug loading efficiency. Herein, DNA framework-based hybrid nanomaterials are rationally engineered by using a molecular docking tool, where the framework acts as a template to support conjugated polymers. The hybrid materials exhibit high stability in biofluids owning to the multiple interactions between DNA and cationic conjugated polymer. Through molecular docking, it is found that a specific structure of the conjugated polymer at major grooves of DNA gives rise to a unique pocket for small-molecular drug doxorubicin (DOX) yielding lower binding energy than conventional DOX binding sites. This increases the binding affinity of DOX, allowing for high drug loading content and efficiency, and preventing drug leakage under physiological condition. As a proof of concept, the hybrid nanomaterials equipped with aptamer are used to carry DOX and antisense oligonucleotide G3139, which effectively inhibits solid tumor growth and shows negligible side effects on mice. It is anticipated that this approach would find broad applications in hybrid materials design and precise medicine.
Keyphrases
- molecular docking
- circulating tumor
- drug delivery
- single molecule
- cell free
- molecular dynamics simulations
- nucleic acid
- photodynamic therapy
- cancer therapy
- emergency department
- gold nanoparticles
- multidrug resistant
- type diabetes
- drug induced
- circulating tumor cells
- mass spectrometry
- high resolution
- insulin resistance
- skeletal muscle
- capillary electrophoresis