SERS nanostructures with engineered active peptides against an immune checkpoint protein

Area of Science:

• Biotechnology and Nanomedicine
• Immunology and Cancer Research

Background:

• The programmed death ligand 1 (PD-L1) protein on tumor cells inhibits CD8+ T-lymphocyte activity by binding to PD-1.
• Targeting the PD-L1/PD-1 interaction is a key strategy in cancer immunotherapy to restore anti-tumor immune responses.

Purpose of the Study:

• To engineer and evaluate gold plasmonic nanostructures functionalized with a peptide (CLP002) for targeting PD-L1.
• To investigate the targeting efficacy of these nanostructures against cancer cells overexpressing PD-L1.

Main Methods:

• Design and synthesis of gold plasmonic nanostructures with surface-enhanced Raman scattering (SERS) properties.
• Functionalization of nanostructures with an engineered peptide (CLP002) targeting PD-L1.
• Molecular dynamics simulations to predict peptide-PD-L1 interactions and experimental validation using MDA-MB-231 cancer cells.

Main Results:

• Molecular dynamics simulations confirmed the specific targeting interaction of CLP002 with PD-L1.
• Experimentally, the functionalized SERS nanostructures demonstrated significant targeting activity against PD-L1-overexpressing MDA-MB-231 breast cancer cells.
• Optimal targeting was observed when CLP002 was linked to the nanostructure surface via a short charged sequence and a long PEG chain.

Conclusions:

• The study successfully developed PD-L1-targeting SERS nanostructures functionalized with the engineered peptide CLP002.
• These functionalized nanostructures represent a promising tool for targeted cancer immunotherapy by modulating the PD-L1 immune checkpoint.