Immobilisation and encapsulation of bioactive molecules
The immobilisation of bioactive molecules on the surface of nanomaterials or encapsulation in porous structures is a facile way to control their biological activity and targeting ability, trap potentially cytotoxic decomposition products, and generate polyfunctional structures for theranostic applications. Such theranostic agents include both bioactive and imaging modalities in a single system and are important to establish novel personalised medical treatment options. In the Schatzschneider group, we have experience in the preparation, characterization, and study of biological activity of both hard and soft nanomaterials.
Our work on hard nanomaterials is mostly related to an on-going interest in CO-releasing molecules (CORMs) as delivery systems for this important small-molecule messenger. Using surface modification of organic and inorganic hard nanomaterials such as nanodiamond or silica particles, respectively, combined with photoinduced CO release allows precise spatial and temporal control of the release process, with potentially cytotoxic byproducts still attached to the surface:
- G. Dördelmann, T. Meinhardt, T. Sowik, A. Krüger, U. Schatzschneider, CuAAC click functionalization of azide-modified nanodiamond with a photoactivatable CO releasing molecule (PhotoCORM) based on [Mn(CO)3(tpm)]+, Chem. Commun. 48, 11528-11530 (2012)
- G. Dördelmann, H. Pfeiffer, A. Birkner, U. Schatzschneider, Silicium dioxide nanoparticles as carriers for photoactivatable CO releasing molecules (PhotoCORMs), Inorg. Chem. 50, 4362-4367 (2011)
Alternatively, carbon monoxide can also be directly encapsulated in the inner porous structure of nanomaterials such as metal-organic frameworks (MOFs) and released upon decomposition of the MOF structure:
- M. Ma, H. Noei, B. Mienert, J. Niesel, E. Bill, M. Muhler, R.A. Fischer, Y. Wang, U. Schatzschneider, N. Metzler-Nolte, Iron metal-organic frameworks MIL-88B and NH2-MIL-88B for the loading and delivery of the gasotransmitter carbon monoxide, Chem. Eur. J. 19, 6785-6790 (2013)
Finally, we have shown that metal-carbonyl complexes covalently attached to a gold surface can be visualized with scattering scanning near-field infrared microscopy (IR s-SNOM, often also abbreviated as s-SNIM) at a lateral resolution of 90 × 90 nm2 based on the inherent vibrational signature of the C-O stretching mode:
- I. Kopf, H.W. Peindy N'Dongo, F. Ballout, U. Schatzschneider, E. Bründermann, M. Havenith, Introducing cymantrene labels into scattering scanning near-field infrared microscopy, Analyst 137, 4995-5001 (2012)
In a recent project, we have also become interested in the modification of gas-filled microbubbles as ultrasound-responsive carrier systems for cytotoxic metal complexes. Composed of a lipid shell encapsulating a core of an inert gas such as octafluoropropane or sulphur hexafluoride, we want to decorate the lipid hull with metal complexes featuring long lipophilic chains in the ligand periphery for strong association with the microbubbles.
At low acoustic pressure, these serve as echocontrast agents and will allow in vivo imaging of the bubble distribution in the body, while at high acoustic pressure, bubble rupture occurs due to inertial cavitation, which leads to release of the bubble "payload" to the surrounding tissue with concomitant opening of cell-cell junction, which is important for example for drug delivery through the blood-brain barrier (BBB):
- V. Mawamba, C. Hagemann, M. Löhr, V. Sturm, U. Schatzschneider, unpublished results