Abstract
Novel surface-functionalized cross-linked nanogels were developed as a platform to allow conjugation of monoclonal antibodies (mAb) for targeted drug delivery. Well-defined diblock copolymers of poly(ethylene glycol)-b-poly(methacrylic acid) (PEG-b-PMA) with PEG terminal aldehyde functionality were synthesized by atom transfer radical polymerization (ATRP) and characterized by GPC and (1)H NMR. These copolymers were used to prepare nanogels via condensation of PEG-b-PMA with Ca(2+) ions into micelle-like aggregates, cross-linking of the PMA/Ca(2+) cores and removal of Ca(2+) ions. The resulting nanogels represent highly swollen spherical polyelectrolyte particles with free terminal aldehyde functionalities at the nonionic PEG chains. A reductive amination reaction between aldehyde groups and amino groups of mAb resulted in effective conjugation to the nanogels of mAb CC49 against tumor-associated glycoprotein 72 (TAG-72). The mAb retained the binding affinity to bovine submaxillary mucin after conjugation as shown by surface plasmon resonance (SPR). Therefore, aldehyde functionalized nanogels can be linked to mAb using a simple, one-step approach. They may have potential for targeted delivery of diagnostic and therapeutic agents to tumors.