A robust and versatile host-guest peptide toolbox for developing highly stable and specific quantum dot-based peptide probes for imaging extracellular matrices and cells

Multiplex fluorescence imaging plays a vital role in precision medicine for targeting complex diseases with diverse biomolecular signatures. Quantum dot (QD) probes with vibrant colors are promising candidates for multiplex imaging, but their stability and specificity are frequently compromised by the current tedious post-modification process. We have herein developed a robust and versatile host-guest peptide (HGP) toolbox for creating highly stable and specific QD-based peptide probes for imaging extracellular matrices and cells. The HGP system comprises a host peptide and a guest peptide with a shared sequence pattern of cysteine and negatively charged amino acids, allowing for QD stabilization and specificity towards targeted biomarkers. HGP has been demonstrated as a convenient one-step approach to construct hydrophilic QD-based peptide probes with superior stability under various conditions. Six multicolor HGP-modified QDs have been developed to specifically target extracellular matrix proteins such as collagen, laminin, and nidogen, as well as major cellular elements like the membrane, nucleus, and cytoplasm, providing an efficient tool for real-time monitoring of high-resolution interactions between cancer cells and the extracellular matrix. The HGP system represents a next-generation approach to developing QDs with unprecedented stability and specificity, holding great potential in multiplex imaging and precision medicine.