Abstract: Multifunctional Mesoporous Nanoparticles for Targeted Drug Delivery

Prof Thomas Bein (Munich)

Mesoporous silica nanoparticles (MSN) have recently attracted much attention as platform for the development of nanoagents for targeted drug delivery, particularly for anti-cancer drugs. The tunable pore system, large pore volume and the ability to integrate multiple organic functionalities in MSN offer great potential for creating novel drug delivery strategies. We will first provide an overview on current research regarding the synthesis of mesoporous nanoparticles, approaches towards targeting certain cell receptors, as well as controlled molecular release systems based on internal (such as pH and redox potential) and external (light, temperature, etc.) stimuli. In the following we will discuss several recent examples from our research addressing the numerous challenges in targeted drug delivery.

We have employed folate and epidermal growth factor (EGF) for successful cell targeting with 70 nm MSN, as well as pH-, redox-, and temperature-responsive release systems. A novel pH-responsive release system has been created based on carbonic anhydrase (CA) gatekeepers (hydrodynamic diameter 5.4 nm). This system relies on the spatial control of functionalization available for our previously developed mesoporous silica core-shell nanoparticles. A pH-dependent CA inhibitor was covalently attached to the surface of the MSN, resulting in the desired opening mechanism triggered by the endosomal pH change.

To induce endosomal escape, we have covalently attached a red-light sensitive phthalocyanine photosensitizer to the MSN, surrounded by a lipid bilayer. Photoactivation leads to endosomal membrane rupture in cells causing cargo release from the mesopores into the cytosol. Alternatively, we have exploited the proton sponge effect during acidification of the endosome with polymer-functionalized MSN to achieve endosomal release.
Finally, it is of great interest to expand the scope of bioactive cargo molecules that can be released from MSN systems. We have developed organically functionalized large-pore MSN that can reversibly adsorb oligonucleotides such as siRNA. The latter is investigated as an alternative therapeutic platform with anticancer activity.

These and other examples show that mesoporous silica nanoparticles represent a promising and flexible platform for numerous biomedical applications.