Parahydrogen-Induced Polarization of a Labeled, Cancer-Targeting DNA Aptamer

Area of Science:

• Biophysical Chemistry
• Molecular Imaging
• Biotechnology

Background:

• Hyperpolarization significantly enhances Nuclear Magnetic Resonance (NMR) signals of biomacromolecules, offering potential for advanced diagnostic applications.
• Achieving parahydrogen-induced polarization (PHIP) in large biomolecules like DNA aptamers is challenging due to required catalytic interactions and solubility issues.

Purpose of the Study:

• To demonstrate the feasibility of hyperpolarizing the cancer-targeting DNA aptamer AS1411 using parahydrogen.
• To identify structural requirements for successful hyperpolarization of DNA aptamers.
• To develop a method for enhancing NMR signals of AS1411 while preserving its biological function for potential diagnostic use.

Main Methods:

• Screening of various molecular motifs for unsaturated labels within nucleosides and DNA oligomers.
• Modification of AS1411 DNA aptamer polarity by complexing the DNA backbone with amino polyethylene glycol (PEG) chains.
• Parahydrogenation of the modified AS1411 aptamer to induce hyperpolarization.

Main Results:

• Identification of specific structural prerequisites for the successful hyperpolarization of the AS1411 DNA aptamer.
• Demonstration of unprecedented hyperpolarization of AS1411 via parahydrogenation.
• Confirmation that DNA structure and biological function are maintained after modification and hyperpolarization.

Conclusions:

• The study successfully achieved hyperpolarization of the AS1411 DNA aptamer, overcoming previous limitations.
• The developed method, involving structural modification and PEGylation, enables stable and functional hyperpolarized DNA aptamers.
• This advancement is expected to significantly contribute to the development of hyperpolarized molecular imaging technologies for improved disease detection.