Mesoporous Silica Nanoparticles

Mesoporous silica nanoparticles (MSNs) are silica nanoparticles containing pores approximately 2–50 nm in diameter, consistent with the IUPAC definition of mesoporosity. Their high internal surface area, tunable pore dimensions, adaptable surface chemistry, and controllable particle architecture make them useful for applications ranging from drug delivery and catalysis to selective adsorption and environmental chemical removal.

MSN performance depends on more than particle diameter alone. Pore size controls which molecules can enter the particle, surface chemistry controls interactions with those molecules, and pore architecture influences how loaded material moves through and exits the particle. nanoComposix develops mesoporous silica with these variables tailored around the intended application.

Need help comparing pore structures and selecting a particle? See the Mesoporous Silica Selection Guide.

How Mesoporous Silica Nanoparticle Design Controls Function

Three closely related design variables determine much of an MSN's behavior: pore size, surface chemistry, and pore architecture. Controlling these characteristics makes it possible to tailor adsorption, loading, molecular selectivity, and release.

Pore Size: Size-Selective Adsorption

MSNs can be synthesized with narrow pore-size distributions, allowing pore dimensions to act as a physical size-selection mechanism. Molecules small enough to enter the pore network can access the internal surface area, while larger molecules can be excluded.

This behavior is useful for applications involving size-selective adsorption and molecular separation.

Surface Chemistry: Functionally Selective Adsorption

The internal and external silica surfaces can also be modified with functional groups selected to interact with particular classes of molecules. For example, positively charged surfaces can increase interactions with negatively charged molecules, while hydrophobic surfaces can promote interactions with hydrophobic species.

Combining pore-size control with tailored surface interactions enables selective adsorption based on both molecular dimensions and chemistry. Applications include hydrophobic drug encapsulation, environmental chemical removal, and other separation or loading processes.

Pore Architecture: Loading & Release

The organization of the pore network can also be varied. Mesoporous silica architectures include MCM-41, MCM-48, radial, cubic, wormlike, and other pore arrangements. The appropriate structure depends on the application because pore connectivity and geometry influence how molecules move through the particle and how readily loaded material can be released.

For example:

• Hexagonal channels: Cargo can enter or leave through either end of an individual channel.
• Cubic networks: Interconnected pores allow molecules to move through a more complex internal network and reach multiple pore outlets.
• Radial pores: Individual channels extend through the particle, requiring material within a given pore to leave through the same channel. This architecture can help limit premature leakage for some encapsulation applications.

Applications of Mesoporous Silica Nanoparticles

The high internal surface area, controllable pore dimensions, and adaptable surface chemistry of MSNs have driven research across biomedical delivery, catalysis, adsorption, separation, and other applications.

Nanomedicine & Drug Delivery

Mesoporous silica nanoparticles have been widely studied as drug-delivery carriers because their pore networks provide high internal surface area for loading while their surfaces can be modified around payload and biological-interaction requirements.^2–4

Pore dimensions can be selected around the size of the intended payload, while internal surface chemistry can be adjusted for molecules with different hydrophilic, hydrophobic, or ionic characteristics. External surface functionalization can also support strategies intended to alter interactions with cells, tissues, or biological components.

MSNs can additionally be engineered with degradable architectures to support release of their contents under selected conditions.⁵ Together, these design variables provide control over loading, retention, release, and particle-surface interactions.

For a deeper look at how pore structure, surface chemistry, and other MSN design variables can be tailored for therapeutic delivery, read Enhancing Therapeutic Delivery with Tunable Mesoporous Silica Nanoparticle Platforms. For broader development support, see Nanomedicine CDMO Services.

Catalysis

Mesoporous silica also provides a high-surface-area scaffold for catalytic materials. Catalysts can be attached to the internal silica surface, incorporated into the MSN structure, or combined with functional groups that participate directly in a reaction.

Narrow pore-size distributions can provide shape or size selectivity by limiting which substrates can reach catalytic sites within the particle. One example is the use of metallocene complexes grafted to mesoporous silica for reactions involving bulky substrates.⁶ Catalytically active inorganic species can also be integrated into mesoporous frameworks, including titanium-containing structures developed for selective oxidation reactions.⁷

Surface-functionalized MSNs can also support acid/base catalysis without transition metals. Bifunctional mesoporous silica containing both acidic and basic groups has been studied for carbonyl activation in Aldol, Henry, and cyanosilylation reactions.⁸

Another practical advantage is that particulate catalysts can be separated mechanically, including by centrifugation, rather than relying exclusively on chemical separation. When the particle and pore framework remain intact, the catalytic material may then be recovered and reused.

How Mesoporous Silica Nanoparticles Are Made

Conventional solid silica nanospheres are commonly synthesized using variations of the Stöber process. Mesoporous silica requires an additional pore-forming template, typically a surfactant, during silica formation.

Surfactants contain both a hydrophobic region and a hydrophilic region. In an aqueous environment, they organize into structures such as micelles to minimize exposure of their hydrophobic portions to water.

During hydrolysis and condensation of the silica precursor under basic conditions, oligomeric silica species containing silanol groups form in solution. Deprotonated silica species can interact with positively charged surfactant assemblies, and continued condensation builds a hybrid inorganic-organic silica network around the surfactant template.

Removing the surfactant after particle formation leaves behind the pore network that defines the mesoporous structure.

Why CTAB Removal Matters

CTAB is a commonly used surfactant template in mesoporous silica synthesis. After synthesis, removing the surfactant is important before the pore network can be fully used, particularly for biological applications.

CTAB removal serves three main purposes:

1. Pore accessibility. Surfactant remaining within the pores occupies internal volume and reduces the space available for loading other molecules.
2. Biological compatibility. CTAB can interact with phospholipid cell membranes and can be cytotoxic at sufficiently high concentrations. Effective removal is therefore especially important when MSNs are being prepared for biological research.
3. Pore-surface modification. Removing the surfactant exposes the internal silica surface for subsequent functionalization, including amination, thiolation, or hydrophobic modification.

Internal and external silica surfaces can also be engineered differently. For example, the pore surface may be functionalized to promote loading of a particular molecule while the exterior carries another functional group for subsequent conjugation or particle-surface modification.

CTAB Removal Methods

The following methods describe approaches used during MSN manufacturing and purification rather than a required preparation step for every purchased material.

Custom Mesoporous Silica Nanoparticles

Mesoporous silica can be engineered across a broad particle-size range and with different pore dimensions, arrangements, surface chemistries, and spatial distributions of porosity. nanoComposix has developed particles ranging from tens to several hundreds of nanometers with architectures including MCM-41 hexagonal and radial pore structures.

The TEM images below compare two mesoporous silica pore geometries available in the nanoComposix portfolio: large-pore radial silica on the left and MCM-41 hexagonal silica on the right.

Spatially Controlled Porosity & Hollow Silica

Porosity can also vary within different regions of the same particle. Examples include hollow particles with mesoporous silica shells, particles with larger hollow interiors and thinner porous shells, and particles with denser cores surrounded by more porous outer regions.

The examples below show 50 nm MSNs with highly porous interiors and a denser outer coating, 500 nm hollow silica nanoparticles, and 500 nm solid silica nanoparticles with mesoporous shells.

Mesoporous-Silica-Shelled Nanoparticles

Mesoporous silica can also be grown around a core composed of another nanomaterial. During surfactant-templated synthesis, inorganic nanoparticles dispersed within the aqueous surfactant system can provide a substrate for silica deposition and growth.

Surfactant associated with the core particle can provide colloidal stabilization while also helping create an interface for hydrolyzed silica species to condense around the underlying nanoparticle.

This approach has been used to prepare mesoporous-silica shells around silver, gold, iron oxide, quantum dots, and other inorganic nanoparticle cores. The TEM image below shows an example of 50 nm gold nanoparticles coated with mesoporous silica.

Core-shell architectures can combine the loading capacity and surface chemistry of mesoporous silica with properties of the underlying core, including plasmonic, fluorescent, photothermal, imaging, or magnetic behavior. These multifunctional structures have been investigated in theranostic and other multimodal nanoparticle systems and can also be extended to different core morphologies.

Large-Pore Mesoporous Silica Nanoparticles

Large-pore and dendritic mesoporous silica structures have received increasing research attention since approximately 2010.^9,11,12 Pore-expansion strategies have used a variety of chemistries, including ring-structured additives such as cyclohexane and trimethylbenzene, chain-structured additives such as octadecene, and anion-assisted approaches using compounds such as sodium salicylate or sodium trifluoroacetate.

These approaches can produce dendritic pores spanning approximately 5–30 nm, extending mesoporous silica to loading applications involving larger molecules and biomolecules.

Selected Literature

Research Featuring nanoComposix Mesoporous Silica

1. Zhao, Q.; Wu, B.; Shang, Y.; Huang, X.; Dong, H.; Liu, H.; Chen, W.; Gui, R.; Li, J. Development of a Nano-Drug Delivery System Based on Mesoporous Silica and Its Anti-Lymphoma Activity. Applied Nanoscience 2020.

References Cited

1. Rouquerol, J.; Avnir, D.; Fairbridge, C. W.; Everett, D. H.; Haynes, J. M.; Pernicone, N.; Ramsay, J. D. F.; Sing, K. S. W.; Unger, K. K. Recommendations for the Characterization of Porous Solids (Technical Report). Pure and Applied Chemistry 1994, 66, 1739–1758.
2. Li, Z.; Barnes, J. C.; Bosoy, A.; Stoddart, J. F.; Zink, J. I. Mesoporous Silica Nanoparticles in Biomedical Applications. Chemical Society Reviews 2012, 41, 2590–2605.
3. Slowing, I. I.; Vivero-Escoto, J. L.; Wu, C.-W.; Lin, V. S.-Y. Mesoporous Silica Nanoparticles as Controlled Release Drug Delivery and Gene Transfection Carriers. Advanced Drug Delivery Reviews 2008, 60, 1278–1288.
4. Argyo, C.; Weiss, V.; Bräuchle, C.; Bein, T. Multifunctional Mesoporous Silica Nanoparticles as a Universal Platform for Drug Delivery. Chemistry of Materials 2014, 26, 435–451.
5. Hao, X.; Hu, X.; Zhang, C.; Chen, S.; Li, Z.; Yang, X.; Liu, H.; Jia, G.; Liu, D.; Ge, K.; et al. Hybrid Mesoporous Silica-Based Drug Carrier Nanostructures with Improved Degradability by Hydroxyapatite. ACS Nano 2015, 9, 9614–9625.
6. Maschmeyer, T.; Rey, F.; Sankar, G.; Thomas, J. M. Heterogeneous Catalysts Obtained by Grafting Metallocene Complexes onto Mesoporous Silica. Nature 1995, 378, 159–162.
7. Corma, A.; Navarro, M. T.; Pariente, J. P. Synthesis of an Ultralarge Pore Titanium Silicate Isomorphous to MCM-41 and Its Application as a Catalyst for Selective Oxidation of Hydrocarbons. Journal of the Chemical Society, Chemical Communications 1994, 147–148.
8. Huh, S.; Chen, H.-T.; Wiench, J. W.; Pruski, M.; Lin, V. S.-Y. Cooperative Catalysis by General Acid and Base Bifunctionalized Mesoporous Silica Nanospheres. Angewandte Chemie International Edition 2005, 44, 1826–1830.
9. Polshettiwar, V.; Cha, D.; Zhang, X.; Basset, J.-M. High-Surface-Area Silica Nanospheres (KCC-1) with a Fibrous Morphology. Angewandte Chemie International Edition 2010, 49, 9652–9656.
10. Chen, F.; Goel, S.; Valdovinos, H. F.; Luo, H.; Hernandez, R.; Barnhart, T. E.; Cai, W. In Vivo Integrity and Biological Fate of Chelator-Free Zirconium-89-Labeled Mesoporous Silica Nanoparticles. ACS Nano 2015, 9, 7950–7959.
11. Shen, D.; Yang, J.; Li, X.; Zhou, L.; Zhang, R.; Li, W.; Chen, L.; Wang, R.; Zhang, F.; Zhao, D. Biphase Stratification Approach to Three-Dimensional Dendritic Biodegradable Mesoporous Silica Nanospheres. Nano Letters 2014, 14, 923–932.
12. Wang, Y.; Song, H.; Yang, Y.; Liu, Y.; Tang, J.; Yu, C. Kinetically Controlled Dendritic Mesoporous Silica Nanoparticles: From Dahlia- to Pomegranate-like Structures by Micelle Filling. Chemistry of Materials 2018, 30, 5770–5776.

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Related mesoporous silica resources

• Mesoporous Silica Selection Guide
• Enhancing Therapeutic Delivery with Tunable Mesoporous Silica Nanoparticle Platforms
• Introduction to Silica Nanoparticles
• Silica Nanoparticle Physical Properties
• Silica Surface Chemistry
• Silica Nanoparticle Applications