Genetically designed biomolecular capping system for mesoporous silica nanoparticles enables receptor-mediated cell uptake and controlled drug release
Language English Country England, Great Britain Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
27021414
DOI
10.1039/c5nr08163g
Knihovny.cz E-resources
- MeSH
- Biological Transport, Active MeSH
- Cell Line MeSH
- Dactinomycin administration & dosage pharmacokinetics MeSH
- HeLa Cells MeSH
- Carbonic Anhydrase II chemistry genetics metabolism MeSH
- KB Cells MeSH
- Drug Delivery Systems * MeSH
- Delayed-Action Preparations MeSH
- Humans MeSH
- Mice MeSH
- Nanoparticles * chemistry MeSH
- Silicon Dioxide MeSH
- Protein Engineering MeSH
- Antineoplastic Agents administration & dosage pharmacokinetics MeSH
- Receptors, Drug chemistry genetics metabolism MeSH
- Drug Liberation MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Dactinomycin MeSH
- Carbonic Anhydrase II MeSH
- Delayed-Action Preparations MeSH
- Silicon Dioxide MeSH
- Antineoplastic Agents MeSH
- Receptors, Drug MeSH
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.
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