Hybrid PNA-peptide hydrogels as injectable CEST-MRI agents

Area of Science:

• Biomaterials Science
• Chemical Biology
• Medical Imaging

Background:

• Peptide self-assembly offers versatile platforms for biomedical applications.
• Chemical Exchange Saturation Transfer (CEST) Magnetic Resonance Imaging (MRI) is a promising metal-free contrast imaging technique.
• Developing novel materials for enhanced MRI contrast and targeted delivery is crucial.

Purpose of the Study:

• To synthesize and characterize peptide nucleic acid (PNA)-modified peptides for biomedical applications.
• To investigate the gelling properties and mechanical responsivity of these peptide-based hydrogels.
• To evaluate the potential of these hydrogels as contrast agents for CEST-MRI and as injectable implants for in vivo cancer detection.

Main Methods:

• Synthesis and characterization of PNA-modified lysine-containing peptides (a-K2, c-K2, g-K2, t-K2).
• Assessment of hydrogel formation and mechanical properties, including Watson-Crick pairing effects.
• CEST-MRI signal generation analysis and in vitro cytocompatibility testing on GL261, TS/a, and 3T3-NIH cell lines.
• In vivo evaluation via intratumor injection in mice bearing TS/a breast cancer xenografts.

Main Results:

• The c-K2 peptide sequence exhibited gelling properties.
• Watson-Crick pairing between c-K2 and g-K2 significantly enhanced hydrogel mechanical responsivity.
• The hydrogel matrices generated a detectable CEST signal around 2.5 ppm from water.
• The materials demonstrated cytocompatibility with tested cancer and fibroblast cell lines.
• Successful in vivo detection was achieved through intratumor injection in a murine breast cancer model.

Conclusions:

• PNA-modified peptide hydrogels can be engineered for tunable mechanical properties and CEST-MRI signal generation.
• These peptide-based matrices are cytocompatible and suitable for in vivo applications.
• The developed materials show promise as injectable implants for enhanced cancer detection using metal-free CEST-MRI.