title: Mesoporous Silica Nanoparticles with Large Pores for the Encapsulation and Release of Proteins.
abstract: Mesoporous silica nanoparticles (MSNs) have been explored extensively as solid supports for proteins in biological and medical applications. Small (<200 nm) MSNs with ordered large pores (>5 nm), capable of encapsulating therapeutic small molecules suitable for delivery applications in vivo, are rare however. Here we present small, elongated, cuboidal, MSNs with average dimensions of 90 × 43 nm that possess disk-shaped cavities, stacked on top of each other, which run parallel to the short axis of the particle. Amine functionalization was achieved by modifying the MSN surface with 3-aminopropyltriethoxysilane or 3-[2-(2-aminoethylamino)ethylamino]propyltrimethoxysilane (AP-MSNs and AEP-MSNs) and were shown to have similar dimensions to the nonfunctionalized MSNs. The dimensions of these particles, and their large surface areas as measured by nitrogen adsorption-desorption isotherms, make them ideal scaffolds for protein encapsulation and delivery. We therefore investigated the encapsulation and release behavior for seven model proteins (α-lactalbumin, ovalbumin, bovine serum albumin, catalase, hemoglobin, lysozyme, and cytochrome c). It was discovered that all types of MSNs used in this study allow rapid encapsulation, with a high loading capacity, for all proteins studied. Furthermore, the release profiles of the proteins were tunable. The variation in both rate and amount of protein uptake and release was found to be determined by the surface chemistry of the MSNs, together with the isoelectric point (pI), and molecular weight of the proteins, as well as by the ionic strength of the buffer. These MSNs with their large surface area and optimal dimensions provide a scaffold with a high encapsulation efficiency and controllable release profiles for a variety of proteins, enabling potential applications in fields such as drug delivery and protein therapy.
authors.forename: Jing
authors.initials: J
authors.lastname: Tu
authors.forename: Aimee L
authors.initials: AL
authors.lastname: Boyle
authors.affiliation: Laboratory of Materials and Interface Chemistry & Center of Multiscale Electron Microscopy, Department of Chemical engineering and Chemistry, and Institute for Complex Molecular Systems, Eindhoven University of Technology , P.O. Box 513, 5600 MB Eindhoven, The Netherlands.
authors.forename: Heiner
authors.initials: H
authors.lastname: Friedrich
authors.affiliation: Laboratory of Materials and Interface Chemistry & Center of Multiscale Electron Microscopy, Department of Chemical engineering and Chemistry, and Institute for Complex Molecular Systems, Eindhoven University of Technology , P.O. Box 513, 5600 MB Eindhoven, The Netherlands.
authors.forename: Paul H H
authors.initials: PH
authors.lastname: Bomans
authors.forename: Jeroen
authors.initials: J
authors.lastname: Bussmann
authors.affiliation: Laboratory of Materials and Interface Chemistry & Center of Multiscale Electron Microscopy, Department of Chemical engineering and Chemistry, and Institute for Complex Molecular Systems, Eindhoven University of Technology , P.O. Box 513, 5600 MB Eindhoven, The Netherlands.
authors.forename: Nico A J M
authors.initials: NA
authors.lastname: Sommerdijk
authors.forename: Wim
authors.initials: W
authors.lastname: Jiskoot
authors.forename: Alexander
authors.initials: A
authors.lastname: Kros
mesh_terms: D016503:Drug Delivery Systems; D053758:Nanoparticles; D016062:Porosity; D011506:Proteins; D012822:Silicon Dioxide
chemical_list: D011506:Proteins; D012822:Silicon Dioxide
keywords: drug delivery; mesoporous silica nanoparticles; nanomedicine; protein loading; protein release; sol−gel