Covalent conjugation of proteins onto fluorescent single-walled carbon nanotubes for biological and medical applications

Single-walled carbon nanotubes (SWCNTs) have optical properties that are conducive for biological applications such as sensing, delivery, and imaging. These applications necessitate the immobilization of macromolecules that can serve as therapeutic drugs, molecular templates, or modulators of surface interactions. Although previous studies have focused on non-covalent immobilization strategies, recent advances have introduced covalent functional handles that can preserve or even enhance the SWCNT optical properties. This review presents an overview of covalent sidewall modifications of SWCNTs, with a focus on the latest generation of “sp(3) defect” modifications. We summarize and compare the reaction conditions and the reported products of these sp(3) chemistries. We further review the underlying photophysics governing SWCNT fluorescence and apply these principles to the fluorescence emitted from these covalently modified SWCNTs. Finally, we provide an outlook on additional chemistries that could be applied to covalently conjugate proteins to these chemically modified, fluorescent SWCNTs. We review the advantages of these approaches, emerging opportunities for further improvement, as well as their implications for enabling new technologies.