Issue 10, 2024

SERS nanostructures with engineered active peptides against an immune checkpoint protein

Abstract

The immune checkpoint programmed death ligand 1 (PD-L1) protein is expressed by tumor cells and it suppresses the killer activity of CD8+ T-lymphocyte cells binding to the programmed death 1 (PD-1) protein of these immune cells. Binding to either PD-L1 or PD1 is used for avoiding the inactivation of CD8+ T-lymphocyte cells. We report, for the first time, Au plasmonic nanostructures with surface-enhanced Raman scattering (SERS) properties (SERS nanostructures) and functionalized with an engineered peptide (CLP002: Trp-His-Arg-Ser-Tyr-Tyr-Thr-Trp-Asn-Leu-Asn-Thr), which targets PD-L1. Molecular dynamics calculations are used to describe the interaction of the targeting peptide with PD-L1 in the region where the interaction with PD-1 occurs, showing also the poor targeting activity of a peptide with the same amino acids, but a scrambled sequence. The results are confirmed experimentally since a very good targeting activity is observed against the MDA-MB-231 breast adenocarcinoma cancer cell line, which overexpresses PD-L1. A good activity is observed, in particular, for SERS nanostructures where the CLP002-engineered peptide is linked to the nanostructure surface with a short charged amino acid sequence and a long PEG chain. The results show that the functionalized SERS nanostructures show very good targeting of the immune checkpoint PD-L1.

Graphical abstract: SERS nanostructures with engineered active peptides against an immune checkpoint protein

Supplementary files

Article information

Article type
Paper
Submitted
12 jan. 2024
Accepted
04 feb. 2024
First published
05 feb. 2024
This article is Open Access
Creative Commons BY-NC license

Nanoscale, 2024,16, 5206-5214

SERS nanostructures with engineered active peptides against an immune checkpoint protein

M. Gobbo, I. Caligiuri, M. Giannetti, L. Litti, C. Mazzuca, F. Rizzolio, A. Palleschi and M. Meneghetti, Nanoscale, 2024, 16, 5206 DOI: 10.1039/D4NR00172A

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