| Abstract No.: | A-F1179 |
| Country: | Canada |
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| Title: | NANOMEDICINE: A FOCUS ON NANOPARTICLES (NP) FOR NON-INVASIVE IMAGING OF CORTICAL GLIA |
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| Authors/Affiliations: | 1 Maik Behrendt*; 1 Ewa Przybytkowski ; 1 Dusica Maysinger;
1 Department of Pharmacology and Therapeutics, McGill University, QC, Canada
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| Content: | Rationale: Nanotechnology in medicine offers a great promise for imaging, diagnosis and therapy of human brain disease and inflammation. However, there is evidence that some luminescent NP can cause oxidative stress and cell death. Astroglia and microglia cells are the principal immune system of the brain responding to stressors by hypertrophy and cytokine release causing additional cell injuries. Furthermore it has been demonstrated that NP induced oxidative stress cause formation of LD. Therefore an in vivo evaluation in real-time is a pre-requiset for acceptance of a NP as a suitable imaging agent.
Objective: The purpose of this study was (i) to conduct a systematic study of a reliable route of non-invasive NP administration to the brain and (ii) to explore mechanisms of interaction of non-functionalized NP with subcellular organelles such as lysosomes, mitochondria and LD in live primary cortical neural cells and in living animals.
Methods: Using intranasal, -oral and –cortical NP administration in wildtype and luciferase expressing transgenic rodents, driven by an astrocyte and microglia specific promoter and live cell fluorescent imaging, requirements for non-invasive glia imaging of inorganic, metal-containing NP in glia cells were assessed.
Results from this study show that (i) far-red emitting OD705 and InGaP/ZnS NP have excellent photophysical properties for repeated real time imaging without causing marked tissue damage (ii) transgenic animals with astroglia and microglia responsive luciferase reporter systems can be exploited for NP-induced glia activation, inflammation and toxicity in vivo (iii) live glia cells rapidly internalize and accumulate NP in distinct cellular compartments, specifically in lysosomes, mitochondria and lipid droplets (LD) and (iv) LD as a dynamic cellular fat accumulating organelle can be utilized as ”a sensor” of NP-induced oxidative stress.
Conclusions: Results from this study suggest that even not readily detectable or even undetectable NP by optical approaches can induce glia cell activation which can have long term consequences on physiological functions in the central nervous system exposed to NP. This approach may be widely applicable for assessing NP distribution and tissue response by formation of LD in live cells and animals and can offer a basis for the design and development of biologically targeted NP for biomedical applications in neurodegenerative disorders.
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