1. Multifunctional Iron-Oxide
Nanoparticle as therapeutic
delivery agent to remove Amyloid-
β aggregates in vitro for Alzheimer’s
disease
BME 626 – Engineering Nanomedical Systems
Tejasvi Parupudi
11.29.2012

2. Contents
• Alzheimer’s disease
• Blood Brain Barrier permeability
• Design and Function of NMS
• Synthesis
• Particle Size and Zeta potential
• AFM image of SPION attachment to Aβ
• Adenosine receptor activation
• In vivo hippocampal section
• Nanotoxicity and Biodistribution
• Organ-on-a-chip
• Issues and improvements

3. Alzheimer’s disease
• Need to study
• Cause- effect
• Existing therapy/solution
• Problems to overcome
• Proposed solution
University of Pittsburgh Medical Center

4. Blood Brain Barrier permeability
• Adenosine receptor activation
• Agonist-Antagonist
• 5′-N-ethylcarboxamidoadenosine (NECA)
• Subtypes
• CD31 Murine Brain Endothelial Cells (Carman et al., 2011)

5. Design and Function of NMS
• Core- SPION
• Coating- Dextran
• Biotinylated Anti-Aβ-Antibody
• MRI agent, less toxic, FDA approved
• Biocompatible, FDA approved
• Targeting CD31 and hCMEC/D3 cell line
• Removal by applied magnetic field
Layer Zeta Potential Size
SPION -5mV 5-10nm
Dextran-SPION -2mV 50nm
Biotin-Ab-D-SPION Net negative ~75nm

6. Synthesis
• Chemical co-precipitation
• Iron stock solution
• 0.1 g Dextran T-10 dissolution
• Biotinylated Ab conjugation
• Verification by TEM and FT-IR spectroscopy
(Kang et al., 2009)
(Lin et al., 2007)

7. Particle Size and Zeta potential
(Lin et al., 2007)

8. AFM image of SPION attachment to Aβ
(Bellova et al., 2010)

9. Adenosine receptor activation
• Streptavidin labeled CD31 MBEC
• Fluorescence In-Situ Hybridizaion and Western
blotting
(Carman et al., 2011).

10. Nanotoxicity and Biodistribution
• Oxidative stress- flow cytometry
• Cell viability- MTT assay
• Sampling blood and CSF
(Apopa et al., 2009)
( Vigor et al., 2010)

11. In vivo hippocampal section
Bynoe lab, Cornell

12. Organ-on-a-chip
•Developmental stage
•Possible elimination of
in vivo
•Microfluidics based
•Basic brain
function/drug response

13. Practical issues
• Passing BBB
• Solution: RMPs (risks such as seizures)
• A1 and A2A and heart(Non-specific interaction)
• Solution: synthetic peptide manufacture
• Dose-dependent manufacture (therapeutically small)
• Solution: prevent disintegration by masking
• Neurotoxicity

14. Present Solution