title: Nanoparticle Assembly of Surface-Modified Proteins.
abstract: Nature's biomaterials such as peptides and proteins represent a valuable source of highly defined macromolecules. Herein we developed a nanoparticle drug delivery system based on the assembly of surface-modified proteins that can be transferred into organic solvents and represent the structural material of the carrier system. The particles are prepared by an oil-in-water nanoemulsion technique without the need of additional denaturation or cross-linking steps for stabilization. We achieve the necessary lipophilic solubility switch of the protein material by high surface PEGylation under conservation of the native three-dimensional protein structure. This study focuses on lysozyme as model enzyme for the preparation of empty and doxorubicin-loaded nanoparticles with an average diameter of 100 nm. The particles are stable in physiological buffers and only release their therapeutic payload into cancer cells after a time-dependent cellular uptake. We also transferred this approach to various proteins, exemplifying the universal applicability of our new preparation method for protein-based nanoparticles.
authors.affiliation: Institut für Pharmazie und Biochemie, Johannes Gutenberg-Universität Mainz , Staudingerweg 5, 55128 Mainz, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Fach
authors.affiliation: Institut für Pharmazie und Biochemie, Johannes Gutenberg-Universität Mainz , Staudingerweg 5, 55128 Mainz, Germany.
authors.forename: Lydia
authors.initials: L
authors.lastname: Radi
authors.affiliation: Institut für Pharmazie und Biochemie, Johannes Gutenberg-Universität Mainz , Staudingerweg 5, 55128 Mainz, Germany.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Wich
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D009113:Muramidase / Q000737:chemistry* / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D013329:Structure-Activity Relationship; D013499:Surface Properties
chemical_list: D004337:Drug Carriers; D004317:Doxorubicin; D009113:Muramidase