Functionalized gold nanoparticles with biomolecules for cancer therapy and neurodegenerative diseases

Design and testing drug delivery systems using biodegradable and bio compatible colloidal carriers made of functionalized gold/polymeric nanoparticles (GNPs) are the vectors of this project. The concept prove will be tested in therapy strategies for cance r and Alzheimer's disease. The project will include the study of functionalized GNPs as photodynamic therapy (PDT) sensitizers being preferentially localized in target tissue, followed by exposure to UV/VIS/IR light or ionizing radiation. The main objecti ve is to develop nanoparticles that increase radiation absorption in diseased areas and minimize damage to normal surrounding tissues. Such enhancement of radiation will benefit cancer patients by decreasing radiation dose and reducing side-effects. Secon dary objectives include i) investigating radiosensitizing potential of coated nanoparticles, ii) combination of nanoparticle-enhanced radiotherapy with the novel drug anti cancer drug/conjugates iii) inhibition of amyloid aggregation by nanoparticles and radiation and iv) inhibitory role of amyloid beta-protein in tumor cell proliferation. The project will contribute to advancing promising delivery systems that can be activated remotely by sensitizing them for light/radiation, and that could prove versati le enough for application to other diseases. The experimental plan: i)Nanoparticle surface functionalization and system characterization ((PEG)-beta-sheet breaker peptide conjugate, anti-oxidants and porphyrins);ii)Interaction mechanism of GNPs with amylo id beta-peptide (Abeta) fibrils;iii) The ability for semiconductor GNPs and their bioconjugates to generate active forms of oxygen for application in PDT;iv)Assess cell uptake and cytotoxicity of nanoparticles in vitro. Our approach is oriented to overcom e two major problems reported: i) short half-life time and the difficulty of bioactive molecules to penetrate cancer tissues or to cross the brain blood barrier; ii) invasive damages on healthy tissues by radiation.