World Health Organization estimates that bloodstream infections affect more than 30 million people worldwide every year causing mortality often due to resistant pathogens. Moreover, heterogeneity of cancer diseases, linked at the crescent cases of manifested neurodegenerative disease, such as Alzheimer disease (AD), are the major expenditure for the public health. Therefore, the costs are predicted to continuously increase over the time due to the necessity of diagnosis and, intensive and prolonged therapies. To reduce health costs, biotechnologies may play a pivotal role by introducing innovative systems cheap and efficient for diagnosis and targeted therapies. In the present work new biosensors and diagnostic/therapeutic systems based on phage display technology are designed and tuned. New specific, selective and robust phage clones are use as probes for both diagnosis and targeted therapies of pathogen bacteria, cancer cells and misfolded Aβ-amyloid structure associated to AD. At this purpose, polymeric platform as well as silica, gold, magnetic and latex nanoparticles are functionalized with specific phage clones and associated at conventional (fluorescence microscopy, E.L.I.S.A., Scannig Electron Microscope SEM) and/or innovative (Raman spectrometry and SERS-Raman) detection systems. In addition, bioactivity of phage clones against pathogen agents, such as P. aeruginosa, as well as inhibition and disaggregation of amyloid β42-induced cytotoxicity are tested in vitro. A new algorithm for the discovery of “self-navigating phage particles” for “smart drug delivery vehicles” is introduced. Finally, in vivo biodistribution in nude mice of phage display f8/9 library are performed to identify peptide home-tissue and home-tumor by qPCR and Next generation sequencing. The results highlight the polyvalent use of phage clones in cheap, innovative and fast detection devices, applicable in several fields (clinical, food and environmental monitoring), as well as in targeted therapy systems for personalized medicine.
|Titolo:||Phage Display as a tool for Marker Discovery, Diagnosis and Targeted Therapy|
|Data di pubblicazione:||8-nov-2019|
|Appare nelle tipologie:||Tesi di dottorato|