Simulation-Guided Rational Design of DNA Walker-Based Theranostic Platform

Area of Science:

• Biomaterials Science
• Nanotechnology
• Molecular Biology

Background:

• Biomolecule-functionalized nanoparticles offer biocompatibility and versatility for biomedical uses.
• DNA-based reactions on nanoparticles are key for biosensors, drug delivery, and biomimetic devices.
• Understanding DNA hybridization on nanoparticles is crucial but currently limited.

Purpose of the Study:

• To investigate the critical factors influencing intermolecular DNA hybridization on nanoparticle surfaces.
• To develop a DNA walker-based smart theranostic platform (DWTP) guided by simulation insights.
• To demonstrate the DWTP's efficacy in miRNA detection, imaging, and targeted gene therapy.

Main Methods:

• Coarse-grained model-based molecular dynamic simulations to study DNA hybridization.
• Development of a DNA walker-based smart theranostic platform (DWTP).
• Application of DWTP for microRNA (miRNA) 21 detection and imaging in a tumor-specific manner.

Main Results:

• Molecular dynamics simulations provided critical insights into "on-particle" DNA hybridization.
• The developed DWTP demonstrated high consistency with simulation predictions.
• DWTP achieved highly sensitive miRNA 21 detection and tumor-specific imaging.
• Precise release of antisense oligonucleotides was achieved, enabling effective gene silencing therapy.
• The platform showed high biosafety and therapeutic efficacy.

Conclusions:

• Simulations of "on-particle" DNA hybridization enhance biosensing performance and therapeutic agent release.
• The DNA walker-based smart theranostic platform represents a novel approach for DNA-based device design.
• This work advances the design and application of nanoparticle-based theranostic systems.