Novel system to achieve one-pot modification of cargo molecules with oligoarginine vectors for intracellular delivery.

There is a growing number of reports showing the usefulness of cell-penetrating peptides (CPPs) including oligoarginines for intracellular delivery of macromolecules. Although the covalent attachment of the CPP segments to the cargo molecules is usually required to ensure effective delivery, conventional methods of conjugation need several manipulation steps that are often time-consuming and laborious. Here, we report a novel approach to allow easy modification of cargo molecules with oligoarginine CPPs. The key feature is the employment of oligoarginines (R8 and R12) equipped with a sulfosuccinimidylsuberyl moiety (BS(3)-R8 and -R12). One-pot modification is achieved simply by mixing BS(3)-R8 and -R12 with cargos in an aqueous buffer. The usefulness of this approach was exemplified through the conjugate formation with Fab fragments of immunoglobulin G, amino-functionalized poly(ethylene glycol)s (amino-PEGs), and amino quantum dots (amino-QDs), yielding an efficient cellular uptake.