Protein A Functionalized Polyelectrolyte Microcapsules as a Universal Platform for Enhanced Targeting of Cell Surface Receptors

Targeted delivery systems recognizing specific receptors are a key element in personalized medicine. Such systems allow the delivery of therapeutics to desired sites of the body, increasing their local concentration and thus reducing the side effects. In this study, we fabricate chemically cross-linked (PAH/PAA)(2) microcapsules coated with specific cell-targeting antibodies in random (via direct covalent coupling to the surface) or optimized (via supporting layer of protein A) orientation. We use these antibody-functionalized capsules to target major histocompatibility complex (MHC) class I receptors in living cells and quantify the efficiency of targeting by flow cytometry. We show for the first time the selective binding of polyelectrolyte microcapsules to MHC class I receptors, and confirm that targeting is allotype-specific. Remarkably, protein A assisted immobilization of antibodies enhances targeting efficiency by 40-50% over capsules with randomly attached antibodies. Moreover, biofunctionalized capsules reveal low levels of cytotoxicity and nonspecific binding, excluding the need of additional modification with poly(ethylene glycol). Thus, protein A coated (PAH/PAA)2 microcapsules represent a unique example of universal targeting tools providing high potential for selective binding to a broad range of cell surface receptors.