Team:SDU-Denmark/Tour72
Medical aspects
For peptide aptamers to be implementable in diagnostics and therapy, some challenges have to be accomodated. Antibodies comprise a dangerous threat for microorganisms displaying pathogen-associated molecular patterns (PAMPs). PAMPs are recognized by the antibodies FabFabfragment, antigen-binding-region and induces an immune response through the FcFcfragment, crystallizable-region, that binds effector cells of the immune system. The effector mechanisms include: OpsonisationOpsonisationOpson originates from Grece, where it referrers to a delicious side-dish. In this context it means that antibodies mark pathogens, making them more appetizing for phagocytes (i.e. neutrophils and macrophages), agglutinationAgglutinationAgglutinare is Latin and means "to glue". In the immune response it means that the antibodies bind multiple antigens, creating a cluster which is easier for the phagocytes to process in one portion instead of one by one. and complement activationComplement SystemWhen the system is activated, several proteases begin to cleave proteins that release certain cytokines, toxic to the pathogen. By a cascade of cleavage reactions the result is the production of a so called cell killing membrane attack complex that will destroy the given microbe. among other reactions.
One example of an effector mechanism could be to attach small gold nanoparticles (sAuNPs). sAuNPs have recently shown to be excellent tools for cancer therapy, especially because of their high biocompatibily, large surface-to-volume ratio and strong diffusivity, which ensure that they remain intact while moving through organisms e.g.
Reference:
Kim CS, et al. Cellular imaging of endosome entrapped small gold nanoparticles, 2015 Jun 10;2:306-15. doi: 10.1016/j.mex.2015.06.001. [PubMed]
By attaching sAuNPs to the peptide aptamer it would be possible to detect and attack pathogenic organisms more precisely, such as cancer cells, instead of using the current method of targeted radioactive therapy where adjacent normal tissue can be seriously damaged too.
Reference:
Thorek DL et al. Reverse-Contrast Imaging and Targeted Radiation Therapy of Advanced Pancreatic Cancer Models. Int J Radiat Oncol Biol Phys. 2015 Jun 9. pii: S0360-3016(15)00612-4.
doi:10.1016/j.ijrobp.2015.06.001 [PubMed]
Chan MD. Recent Technical Advances and Indications for Radiation Therapy in Low-Grade Glioma. Semin Radiat Oncol. 2015 Jul;25(3):189-96.
doi: 10.1016/j.semradonc.2015.02.001
[PubMed]
If peptide aptamer were to be used in such way it would require them to be tolerated by the immune system.
Immunogenicity is a reaction that will occur if the human immune system gets provoked by some foreign microorganism. The bigger molecule the larger risk of immunogenicity. If the immune system develops immunization against the peptide aptamer it will not have any function at all.