Thiolated Nanoparticles for Biomedical Applications: Mimicking the Workhorses of Our Body

Advances in nanotechnology have generated a broad range of nanoparticles (NPs) for numerous biomedical applications. Among the various properties of NPs are functionalities being related to thiol substructures. Numerous biological processes that are mediated by cysteine or cystine subunits of proteins representing the workhorses of the bodies can be transferred to NPs. This review focuses on the interface between thiol chemistry and NPs. Pros and cons of different techniques for thiolation of NPs are discussed. Furthermore, the various functionalities gained by thiolation are highlighted. These include overall bio- and mucoadhesive, cellular uptake enhancing, and permeation enhancing properties. Drugs being either covalently attached to thiolated NPs via disulfide bonds or being entrapped in thiolated polymeric NPs that are stabilized via inter- and intrachain crosslinking can be released at the diseased tissue or in target cells under reducing conditions. Moreover, drugs, targeting ligands, biological analytes, and enzymes bearing thiol substructures can be immobilized on noble metal NPs and quantum dots for therapeutic, theranostic, diagnostic, biosensing, and analytical reasons. Within this review a concise summary and analysis of the current knowledge, future directions, and potential clinical use of thiolated NPs are provided.