The research group of Dr. Christoph Rehbock focuses on the utilization of laser-fabricated metal and alloy nanoparticles in different fields of biomedicine. These nanoparticles are particularly useful in biomedical science as they can be obtained at high purity and are initially ligand free. This allows their efficient functionalization with specific biomolecules, their integration into matrices and their deposition on surfaces with high efficiency, while on the other hand potentially toxic side effects, originating e.g. from artificial ligands during chemical synthesis can be avoided. Furthermore, the laser-based production process offers an outstanding material variety, which allows the facile fabrication of alloy nanoparticles with well controlable composition. Recently, the group has extended its research to organic nanoparticles, applicable as drugs or food additives.The primary research topics in the Nano-Bio group are:
1) Size and composition controlled nanomaterials for Bioimaging, Diagnostics and Biosafety
The Rehbock group develops metal and espacially alloy nanoparticles (e.g. FeAu, AgAu, PtAu) tuned for specific optical features (surface plasmon resonance) as well as magnetic properties. This entails a controlled variation of the particle composition by choice of the target and the solvent in correlation with efficient size control strategies. Another research area involves the synthesis of non plasmonic metal nanoclusters. In contrast to nanoparticles these nanoclusters only consist of a few metal atoms and are designed and studied for their characteristic photoluminescence properties . Furthermore, the group has generated a variety of metal and alloy nanoparticles as reference materials for biosafety evaluations.
2) Nano-bio-conjugates for drug delivery and therapy
The group uses metal and alloy nanoparticles as a platform for a variety of biomolecules and drugs, which are directly coupled to the metal surfasce, predominatly via thiol chemistry. This includes the coupling of nucleotides, peptides, proteins as well as small functional molecules to the particle´s surface, while the parallel arrangement of multiple different ligands on one particle as well as a precise control of surface coverage are vital. These nanobioconjugates can be used as functional components in bioassays and as platforms for photo-induced drug delivery. Furthermore, they may serve as potential nanodrugs counteracting protein misfolding in neurodegenerative diseases like Alzheimer´s disease.
3) Nanoparticle imobilization- nanocomposites and coatings
Another focus of the Nano-Bio team is the immobilization of ligand-free nanoparticles in a polymer matrix forming nanocomposite materials. Here the nanoparticles are embedded into the polymer via a specialized in situ embedding procedure (= laser synthesis of particles directly in the monomer or polymer solution). In this context, the embedded nanoparticles can alter the surface charge of the polymer and serve as a source for the release of biofunctional metal ions. These novel biomaterials were demonstrated to improve cellular growth and proliferation and can be utilized in tissue engineering and implant design. In another approach we examine the immobilization of metal nanoparticles on the surface of neural electrodes, utilizing the electrophoretic deposition (EPD) technique. These electrodes are routinely applied during the treatment of neurological movement disorders like Parkinson´s disease. Central aim in this context is to examine how nanoscopic coatings stabilize and potentially decrease the electrode´s impedance in order to improve the stimulation efficiency of the electrode and prolong battery lifetime in long term stimulation application in vivo.
4) Nanoparticles in proton therapy
A common treatment technique for cancer is radiation therapy which is often done with x-rays having the disadvantage of also irradiating healthy tissue due to a high entrance and exit dose. This is particularly problematic close to sensitive organs or in the still-developing tissue of children. Nowadays, proton therapy is a clinically used alternative, where due to the dependence of the proton´s energy deposition to their velocity, the dose can be precisely distributed in the tumor tissue. Biocompatible noble metal nanoparticles like platinum and gold can function as sensitizers for proton therapy and increase the efficiency of the treatment. This was evidenced in vitro and in vivo, but the mechanism behind the increase is not fully elucidated yet and the transfer of these sensitizers to the clinic is underexplored. Thereto, we investigate the interaction between noble metal nanoparticles and the solvent during proton irradiation using surfactant-free nanoparticles produced through laser-based methods. Here, the absence of organic ligands leads to an increase in efficacy and eases the modeling of the fundamental reactions at the nanoparticle-solvent interface upon proton irradiation based on the catalytic generation of reactive oxygen species (ROS). The main goals of our research are: A) To elucidate the mechanism behind the enhanced ROS generation and herein establish model systems based on fluorescent markers and DNA cleavage in water and hydrogel phantoms, B) the optimization of irradiation parameters like physical dose, particle dose, size and material, and C) the transfer of nanoparticle-based sensitizers to cell culture and in vivo models and the investigation of their clinical applicability.
5) Laser-generated organic nanoparticles
The fabrication of organic nanoparticles by laser fragmentation in liquids has been recently added as a research focus of the group with special emphasis on drugs and food additives. Here, laser processing and size reduction leads to a higher total surface area, which goes along with e.g. an improved solubility and better bioavailability. By using lasers, we generate high-purity aqueous nanoformulations that are directly available as stable colloids. We work with different advanced laser setups to optimize the fragmentation process and achieve high yields of small particles.