Pt–S Bond‐Mediated Nanoflares for High‐Fidelity Intracellular Applications by Avoiding Thiol Cleavage

Abstract The Au−S bond is the classic way to functionalize gold nanoparticles (AuNPs). However, cleavage of the bond by biothiols and other chemicals is a long‐standing problem hindering practical applications, especially in cells. Instead of replacing the thiol by a carbene or selenol for stronger adsorption, it is now shown that the Pt−S bond is much more stable, fully avoiding cleavage by biothiols. AuNPs were deposited with a thin layer of platinum, and an AuNP@Pt‐S nanoflare was constructed to detect the miRNA‐21 microRNA in living cells. This design retained the optical and cellular uptake properties of DNA‐functionalized AuNPs, while showing high‐fidelity signaling. It discriminated target cancer cells even in a mixed‐cell culture system, where the Au‐S based nanoflare was less sensitive. Compared to previous methods of changing the ligand chemistry, coating a Pt shell is more accessible, and previously developed methods for AuNPs can be directly adapted.