An Orthogonal Nucleic Acid/Peptide Amplification Circuit Enables Protease-Triggered, Cancer Cell-Selective PD-L1...

Area of Science:

• Biomedical Engineering
• Molecular Imaging
• Nanobiotechnology

Background:

• Molecular imaging is crucial for detecting programmed death-ligand 1 (PD-L1) in situ.
• Distinguishing PD-L1 expression in malignant versus normal cells presents a significant imaging challenge.
• Current methods lack the specificity required for precise cancer cell visualization.

Purpose of the Study:

• To develop a cancer-selective imaging strategy for PD-L1.
• To engineer a system that differentiates PD-L1 expression on cancer cells versus normal cells.
• To enable non-invasive assessment of tumor response to therapy.

Main Methods:

• An orthogonal nucleic acid/peptide amplification circuit was designed.
• The circuit integrates protease-activated hybridization chain reaction (HCR) with aptamer-mediated target recognition.
• PD-L1 aptamer initiates HCR, while protease-cleavable peptides regulate initiator activity in the tumor microenvironment.

Main Results:

• The system achieved protease-mediated activation of HCR amplification specifically at PD-L1-expressing cancer sites.
• Normal tissues showed minimal HCR activity due to the absence of relevant proteases, enhancing spatial selectivity.
• The strategy enabled non-invasive assessment of tumor responses to immune checkpoint blockade therapy in mouse models.

Conclusions:

• This novel approach provides enhanced spatial selectivity for cancer-specific PD-L1 imaging.
• The methodology bridges DNA nanobiotechnology and peptide biochemistry for advanced biomedical applications.
• It offers a promising tool for evaluating therapeutic efficacy in cancer treatment.