Bio-Click Chemistry: Enzymatic Functionalization of PEGylated Capsules for Targeting Applications

摘要

Targeted delivery with nanoengineered biofunctionalized pharmaceutical carriers has the potential to maximize the uptake of drugs at a diseased site while minimizing therapeutic side effects. Effective drug delivery can be significantly enhanced through covalent and site-specific protein immobilization on the carrier vehicles, as this approach avoids random orientation and inactivation of cell-targeting ligands/ antibodies. Although covalent biofunctionalization can be readily performed on protein functional groups using carbo-diimide-and maleimide-based methods, these approaches do not provide site-directed attachment owing to the abundance of protein functional groups. Advanced techniques such as click chemistry have been commonly used for site-specific immobilization; however, this method requires the incorporation of synthetic functional groups into biomolecules. More recently it has been demonstrated that antibodies expressed as fusion proteins with a SNAP tag (O6-alkylgua-nine-DNA alkyltransferase) can be coupled to O6-alkyl-guanine modified particles.' Other enzyme-based coupling approaches have also been reported for site-selective conjugation but are limited due to the large size of the fusion proteins and the multiple preparation steps.' Hence, there remains a need for an efficient method for the covalent and site-specific functionalization of drug carriers.