Genetically designed biomolecular capping system for mesoporous silica nanoparticles enables receptor-mediated cell uptake and controlled drug release

TL;DR

This paper introduces a genetically engineered enzyme-based capping system for mesoporous silica nanoparticles that enables targeted, receptor-mediated drug delivery and controlled release, enhancing precision in biomedical applications.

Contribution

The study presents a novel enzyme-based cap system with bio-orthogonal click chemistry for targeted drug delivery using genetically modified enzymes with unnatural amino acids.

Findings

Successful delivery of Actinomycin D to KB cells

Receptor-mediated cell uptake demonstrated

Modular platform for theranostics established

Abstract

Effective and controlled drug delivery systems with on-demand release and targeting abilities have received enormous attention for biomedical applications. Here, we describe a novel enzyme-based cap system for mesoporous silica nanoparticles (MSNs) that is directly combined with a targeting ligand via bio-orthogonal click chemistry. The capping system is based on the pH-responsive binding of an aryl-sulfonamide-functionalized MSN and the enzyme carbonic anhydrase (CA). An unnatural amino acid (UAA) containing a norbornene moiety was genetically incorporated into CA. This UAA allowed for the site-specific bio-orthogonal attachment of even very sensitive targeting ligands such as folic acid and anandamide. This leads to specific receptor-mediated cell and stem cell uptake. We demonstrate the successful delivery and release of the chemotherapeutic agent Actinomycin D to KB cells. This novel nanocarrier concept provides a promising platform for the development of precisely controllable and highly modular theranostic systems.