Plug-and-Playable Mesoporous Silica Nanoparticle For Versatile Targeted Drug Delivery

Abstract

For effective drug delivery using nanoparticles, antibody can be beneficially utilized thanks to its high binding affinity to the target site. However, a conventional method to conjugate antibody to nanoparticles involves a multi-step synthetic process, which can damage the antibody’s intrinsic target-recognition nature. Herein, we report a facile approach to construct an antibody-assisted delivery system with high targeting efficiency by achieving direct binding of unmodified pristine antibodies to the nanoparticle surface via simple biomolecular interactions. Mesoporous silica nanoparticles (MSNs) are adopted as a drug-loadable host material, of which external surface is coated with a functional fusion protein consisting of glutathione-S-transferase (GST) and the antibody-binding domain (ABD) called Z domain. It is demonstrated that the Z domain-functionalized MSNs (Z-MSNs) can readily capture antibodies through the Fc regional binding sites and that the antibody-particle binding can be highly stabilized under control of the surface ABD density, against antibody dissociation and exchange with external antibodies. Antibodies can be selectively chosen according to the target and directly applied to Z-MSNs in order to construct a single- or dual-targeting system for enhanced intracellular delivery of pore-loaded drugs to treat cancer. Along with the animal studies showing successful tumoral accumulation and therapeutic activities of antibody-plugged Z-MSNs, the presented results prove a highly facile, efficient, and extensive feature of our delivery platform for a variety of targeted disease treatment.