Activatable iRGD-based peptide monolith: Targeting, internalization, and fluorescence activation for precise tumor...

Area of Science:

• Biomedical Engineering
• Molecular Imaging
• Nanotechnology

Background:

• The internalizing RGD (iRGD) peptide targets αv integrins and penetrates tumors via CendR motif cleavage.
• Current imaging probes often lack specificity and can suffer from high background noise.
• Developing activatable probes that respond to the tumor microenvironment is crucial for precise diagnosis.

Purpose of the Study:

• To design and evaluate an iRGD-based monolithic imaging probe with activatable fluorescence signaling.
• To integrate cancer-specific targeting, internalization, and fluorescence activation into a small peptide framework.
• To assess the probe's performance in vitro and in vivo for tumor imaging.

Main Methods:

• Conjugation of a fluorescent dye and a quencher to the iRGD peptide to create an activatable probe.
• Investigating the dual cleavage requirements (reductive and proteolytic) for fluorescence activation.
• Evaluating probe performance in vitro and in vivo, assessing tumor targeting, penetration, and fluorescence recovery.
• Comparing the activatable probe with a control probe lacking a quencher.

Main Results:

• The developed probe requires dual cleavage of disulfide and amide bonds for fluorescence activation.
• Fluorescence recovery was dependent on tumor-related receptors (αvβ3 integrin and neuropilin-1) in vitro and in vivo.
• The activatable probe visualized tumors more precisely with lower background noise compared to the control probe.
• The probe exhibited minimal in vitro and in vivo toxicity.

Conclusions:

• The iRGD-based activatable monolithic peptide probe demonstrates multifunctional responses specific to the tumor microenvironment.
• The probe offers precise tumor visualization with reduced background noise, enhancing diagnostic accuracy.
• This peptide probe holds significant potential as a next-generation imaging agent for accurate tumor diagnosis.