| Summary: |
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 cancer and Alzheimer's disease. The aim is to develop functionalized gold core nanoparticle/polymeric shell. A foreseeing objective is to demonstrate how these nanocarriers are vehicles for selective controlled release of bioactive molecules. 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 [JuChSuCoGeGeCh08]. The main objective 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. Secondary objectives include:
i) investigating radiosensitizing potential of different nanoparticles (gold/polymeric coated nanoparticles) and selecting most efficient candidate(s), 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 versatile enough for application to other diseases [GhHaDeKiRo08].
The experimental plan :
i) Synthesis of gold nanoparticles to be used as core/vectors for bioactive molecules' stabilization and transport.
ii) Nanoparticle surface functionalization and system characterization to attach the corresponding bioactive molecules. GNPs with polyelectrolyte layers and polysorbates, namely polysorb  |
Summary
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 cancer and Alzheimer's disease. The aim is to develop functionalized gold core nanoparticle/polymeric shell. A foreseeing objective is to demonstrate how these nanocarriers are vehicles for selective controlled release of bioactive molecules. 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 [JuChSuCoGeGeCh08]. The main objective 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. Secondary objectives include:
i) investigating radiosensitizing potential of different nanoparticles (gold/polymeric coated nanoparticles) and selecting most efficient candidate(s), 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 versatile enough for application to other diseases [GhHaDeKiRo08].
The experimental plan :
i) Synthesis of gold nanoparticles to be used as core/vectors for bioactive molecules' stabilization and transport.
ii) Nanoparticle surface functionalization and system characterization to attach the corresponding bioactive molecules. GNPs with polyelectrolyte layers and polysorbates, namely polysorbate 80, will be used to transport the bioactive molecule, (poly
(ethylene glycol) (PEG)-beta-sheet breaker peptide conjugate [RoCaBoPeSaCo09], anti-oxidants and photosensitizers (porphyrins).
iii) Interaction mechanism studies of the conjugate linked to the GNPs with amyloid beta-peptide (Abeta) fibrils.
iv) Study of the ability for semiconductor GNPs and their bioconjugates to generate active forms of oxygen [singlet oxygen and superoxide] for application in PDT [JuChSuCoGeGeCh08];
v) Assess cell uptake and cytotoxicity of nanoparticles in vitro; brain capillary endothelial cell uptake before and after radiation will be visualized.
Our approach is oriented to overcome three major problems reported in other research works:
i) the large size of nanoparticles already developed and particle aggregation [RoHa08]; ii) short half-life time and the difficulty of bioactive molecules to penetrate cancer tissues or to cross the brain blood barrier (BBB) [ka01]; iii) invasive damages on healthy tissues by radiation [JuChSuCoGeGeCh08].
The project will cover the necessary steps to achieve a complete proof of concept, including to assess the activity of molecules (peptide conjugates) tested by the project team [RoCaBoPeSaCo09], when attached to the GNPs for treatment of Alzheimer's disease and cancer [JuChSuCoGeGeCh08]. |