Switchable mesoporous nanoconstructs for controlling cell functions in space and time

This research project was completed in the last funding period.

Project history

The topic of our project B05, comprising the two funding periods, focused on the synthesis of novel porous multifunctional nanoagents and their application for controlling cell functions in space and time.

We have directed our research efforts towards two major topics:
a) the continuous development of multifunctional, biocompatible and degradable nanoagents in form of porous nanoparticles, comprising a range of particle compositions that allow for efficient uptake of guest molecules of varying size and surface properties into their internal cavity system to ensure their stabilization against degradation, and
b) utilization of our nanoagents as delivery agents for guest molecules into cellular environments, enabling a timely and sufficient release and thus controlling cell behavior for therapeutic and/or diagnostic applications.
Considering the design of multifunctional nanoagents, we have greatly extended the development of our established mesoporous silica nanoparticles (MSNs) in different directions and have additionally created completely new porous nanoagents of various compositions. Thus, we have now established:
- mesoporous silica nanoparticles with new morphologies and newly added functionalities (MSN) [1, 12-13]
- new mesoporous silica nanoparticle hybrids in form of organosilicas containing bridging curcumin entities (MCN) [14]
- newly developed porous crosslinked cyclodextrin nanoparticles (CD-NP) [2]
- newly developed porous calcium phosphate citrate nanoagents (CPC-NP) [15]
- functionalized metalorganic porous frameworks (MOF) [3,4,16]
- bimodal mesoporous carbon nanospheres (MCS) [5]
These novel nanoagents enabled the uptake and cellular delivery of a variety of guest molecules, such as:
small molecules: the anticancer agents doxorubicin (CD-NP, [2]) and actinomycin D (MSN, [6]), immunotherapeutics (resiquimod in MSN, Gößl, in progress) or model compounds in form of dye molecules (calcein in MCS, [5]; rhodamin B in CD-NP, [14]; fluorescein in MSN, [17]) as well as covalently anchored dye molecules for particle tracking (MSN, [18])
medium-sized molecules: silencing RNA molecules (siRNA in MSN, [7]; miRNA200c in MSN, Haddick, in progress)
large molecules: enzymes (in MSN, [19]) or antibodies (chromobodies in MSN, [8])
Besides extensive in vitro investigations of particle-cell interactions of the above systems, we have also performed in vivo studies on the anti-cancer effect of CPC-nanoparticles (see patent application [11], and a recent manuscript [15]. Ongoing in vivo studies are also being performed, using MSNs for the delivery of the immuno-stimulant R848 (resiquimod) as a prospective anti-cancer vaccine.
Specific attention was further paid to the biocompatibility of these nanoagents with respect to cell interactions (MOF, [20]; MSN, [21]; MSN, [9]). A comprehensive overview over the unprecedented richness regarding morphology and chemical composition of silica mesoporous nanoparticles and their potential for drug delivery purposes was published as a tutorial review (MSN, [10]).
In summary, we have published 19 papers in peer reviewed journals and have filed 1 patent application. One additional manuscript has been submitted, and ongoing research is performed on 4 different topics.