A Vesicle Supra‐Assembly Approach to Synthesize Amine‐Functionalized Hollow Dendritic Mesoporous Silica Nanospheres for Protein Delivery

Abstract

Intracellular delivery of proteins is a promising strategy of intervention in disease, which relies heavily on the development of efficient delivery platforms due to the cell membrane impermeability of native proteins, particularly for negatively charged large proteins. This work reports a vesicle supra-assembly approach to synthesize novel amine-functionalized hollow dendritic mesoporous silica nanospheres (A-HDMSN). An amine silica source is introduced into a water-oil reaction solution prior to the addition of conventional silica source tetraethylorthosilicate. This strategy favors the formation of composite vesicles as the building blocks which further assemble into the final product. The obtained A-HDMSN have a cavity core of ≈170 nm, large dendritic mesopores of 20.7 nm in the shell and high pore volume of 2.67 cm g . Compared to the calcined counterpart without amine groups (C-HDMSN), A-HDMSN possess enhanced loading capacity to large negative proteins (IgG and β-galactosidase) and improved cellular uptake performance, contributed by the cationic groups. A-HDMSN enhance the intracellular uptake of β-galactosidase by up to 5-fold and 40-fold compared to C-HDMSN and free β-galactosidase, respectively. The active form of β-galactosidase delivered by A-HDMSN retains its intracellular catalytic functions.

Electron Tomography: A Unique Tool Solving Intricate Hollow Nanostructures

“…[65] Nanostructures engineered on the shell of silica hollow spheres, such as mesopores [66] and surface roughness, [67] are usually recognized rather important for biomedical applications, as it is the surface of a nanoparticle that first interacts with biomolecules/biosystems. [65] Nanostructures engineered on the shell of silica hollow spheres, such as mesopores [66] and surface roughness, [67] are usually recognized rather important for biomedical applications, as it is the surface of a nanoparticle that first interacts with biomolecules/biosystems.…”

“…In this regard, the ET analysis with direct measurement through the consecutive tomograms or the 3D rendering of target object offers reliable information of interest, such as spatial configuration, [30,130] particle size, [131] void space dimensions, [66,132,133] porosity, [63] and element content/distribution. However, 2D images derived from conventional EM analysis typically render the spatial information flattened and overlapped, in most cases, providing misleading information.…”

The pore size of mesoporous silica nanoparticles regulates their antigen delivery efficiency

“…Mesoporous silica nanoparticles (MSNs) have been extensively studied as vaccine delivery system because of their advantages including ultrahigh specific surface area, easiness for surface modification, adjustable particle size, and excellent biocompatibility (17)(18)(19)(20)(21)(22). In addition, MSNs contain negatively charged and hydrophilic silanol groups (Si-OH) on their surface, making MSNs a potential lymph node-targeting carrier.…”

Inorganic Nanocrystals Functionalized Mesoporous Silica Nanoparticles: Fabrication and Enhanced Bio-applications

“…Such large-pore mesoporous silica coating may be used for loading of larger molecules, RNA, proteins, etc. (Shen et al, 2014 ; Xu et al, 2015 ; Yang et al, 2015 ; Meka et al, 2016 ; Zhang et al, 2016 ).…”