Visiting Researcher Professor Sergey Deyev delivered a seminar at Macquarie Node entitled: Multifunctional nanoconstructs for bioimaging and therapy.
Summary: Numerous self-assembly systems have been designed, which allow for control of assembly-disassembly with relatively gentle stimuli. These have applications for the construction of “smart” materials for a number of applications (drug delivery, biosensors, etc.). We address the stability of the barnase−barstar system (BBS) -“glued” assemblies subject to destruction. To this end, we test their behavior under severe protein denaturing conditions such as high temperature and low pH as well as high salt and chaotropic agent (urea and guanidinium hydrochloride) concentrations.
Alternatively, it is desirable to design materials that are hard to disassemble. For example, self-assembled multifunctional theranostic agents are expected to demonstrate significant stability to ensure retention of all functional modules within a single entity to be able to perform all programmed functions e.g., imaging, drug delivery, stimulus-responsiveness. We studied such robust protein-assisted nanoparticle self-assembly systems based on barnase-barstar, streptavidin-biotin, antibody-antigen, and protein A-immunoglobulin interactions. The barnase-barstar pair is particularly advantageous due to its productions by genetic engineering. N- and C-termini of both proteins are not involved in the molecular interface of the proteins within the complex, so they are available for fusions such as those with antibodies, fluorescent proteins, and bacterial toxins, which can be used as additional functional modules of the hybrid protein-particle constructions.
The results on applications of barnase-barstar platform with important types of the nanoparticles, including quantum dots, luminescent nanodiamonds, colloidal gold, magnetic NPs, luminescent upconversion NPs as well as delivery of pseudomonas exotoxin A and radioisotope to the HER2/neu overexpressing human adenocarcinoma cells are presented.