Mesoporous Silica Nanoparticle Nanocarriers: Biofunctionality and Biocompatibility

Abstract

The study of ordered mesoporous silica materials has exploded since their discovery by Mobil researchers 20 years ago. The ability to make uniformly sized, porous, and dispersible nanoparticles using colloidal chemistry and evaporation-induced self-assembly has led to many applications of mesoporous silica nanoparticles (MSNPs) as “nanocarriers” for delivery of drugs and other cargos to cells. The exceptionally high surface area of MSNPs, often exceeding 1000 m2/g, and the ability to independently modify pore size and surface chemistry, enables the loading of diverse cargos and cargo combinations at levels exceeding those of other common drug delivery carriers such as liposomes or polymer conjugates. This is because noncovalent electrostatic, hydrogen-bonding, and van der Waals interactions of the cargo with the MSNP internal surface cause preferential adsorption of cargo to the MSNP, allowing loading capacities to surpass the solubility limit of a solution or that achievable by osmotic gradient loading. The ability to independently modify the MSNP surface and interior makes possible engineered biofunctionality and biocompatibility. In this Account, we detail our recent efforts to develop MSNPs as biocompatible nanocarriers (Figure ) that simultaneously display multiple functions including (1) high visibility/contrast in multiple imaging modalities, (2) dispersibility, (3) binding specificity to a particular target tissue or cell type, (4) ability to load and deliver large concentrations of diverse cargos, and (5) triggered or controlled release of cargo. Toward function 1, we chemically conjugated fluorescent dyes or incorporated magnetic nanoparticles to enable in vivo optical or magnetic resonance imaging. For function 2, we have made MSNPs with polymer coatings, charged groups, or supported lipid bilayers, which decrease aggregation and improve stability in saline solutions. For functions 3 and 4, we have enhanced passive bioaccumulation via the enhanced permeability and retention effect by modifying the MSNP surfaces with positively charged polymers. We have also chemically attached ligands to MSNPs that selectively bind to receptors overexpressed in cancer cells. We have used encapsulation of MSNPs within reconfigurable supported lipid bilayers to develop new classes of responsive nanocarriers that actively interact with the target cell. Toward function 4, we exploit the high surface area and tailorable surface chemistry of MSNPs to retain hydrophobic drugs. Finally, for function 5, we have engineered dynamic behaviors by incorporating molecular machines within or at the entrances of MSNP pores and by using ligands, polymers, or lipid bilayers. These provide a means to seal-in and retain cargo and to direct MSNP interactions with and internalization by target cells. Application of MSNPs as nanocarriers requires biocompatibility and low toxicity. Here the intrinsic porosity of the MSNP surface reduces the extent of hydrogen bonding or electrostatic interactions with cell membranes as does surface coati...

Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release

“…In proof-of-concept experiments, we evaluated several candidate systems at the nanoscale level-such as liposomal-based NPs, AuNP, mesoporous silica nanoparticles (MSNPs) (23), and phage-based systems-because they may be targeted by a ligand to a defined cell membrane receptor. HSLs were initially chosen because delivery of their contents can be triggered through temperature-sensitive mechanisms and, by formulating them with lipids with established phase-transition temperature (SI Materials and Methods), cargo release may be more finely tunable.…”

“…A major advantage of MSNPs, which are negatively charged at neutral pH (pK a = 3, ζ-potential = −35.2 mV) due to deprotonation of surface silanols (≡Si-OH), is that their internal porosity provides an enormous surface area (>1,000 m 2 /g) on which to adsorb disparate types of cargo combinations through van der Waals, electrostatic, or hydrogen-bonding interactions (23). Previous reports have shown that owing to the high pK a of dox (8.25), it electrostatically associates with the negatively charged MSNP, resulting in orders of magnitude greater loading than in standard liposomes (35).…”

Protein-gold clusters-capped mesoporous silica nanoparticles for high drug loading, autonomous gemcitabine/doxorubicin co-delivery, and in-vivo tumor imaging

“…[26][27][28][29][30][31][32][33][34] MSN are biocompatible nanomaterials [35,36] and possess disctinctive characteristics such as their tunable porosity and particle size, versatile inner and outer surface chemistry, and capacity to transport and deliver various cargos make these scaffolds ideal drug delivery systems. [37,38] Both molecular and supramolecular nanomachines have been designed with MSN to precisely control the release of guest molecules from their nanopores upon various stimuli including pH, [39,40] one- [41,42] and two-photon irradiation, [43][44][45] enzymes [46,47] and redox processes.…”

Magnetic surfactants

“…While structuring inorganic material with surfactants is well established [65], this concomitant magnetization is a new concept. Such materials are of fundamental interest as they combine high surface area and pore volume with magnetic responsivity with potential applications in catalysis and separations, as well as for simultaneous MR imaging and drug delivery [66]. The authors used a sol-gel technique to template the silica followed by removal of the surfactant cation by exposing to an atmosphere of trimethylamine with moderate heating.…”