Prof. Shai Rahimipour, Bar Ilan University

Surface-Modified Proteinous Microspheres and Selfassembled Cyclic D,L-a-Peptides as Potential Therapeutics
for Alzheimer’s Disease
Prof. Shai Rahimipour
Department of Chemistry
Bar-Ilan University, Israel
E-Mail: [email protected]
Biomaterials for treatment and prevention of
Alzheimer’s disease - NMP 12 – 2015
Alzheimer ’ s disease (AD) is an irreversible,
progressive brain disease that slowly destroys
memory and cognition.
AD currently affects 12 million people worldwide and
it is likely to triple by 2050.
Only few diagnostic agents are available for early
diagnosis of AD.
•
•
Extracellular deposition of senile plaques produced
from Amyloid-β protein (Aβ).
Intracellular formation of neurofibrillary tangles
generated from the microtubule-associated Tau
protein.
•
Dr. Alois Alzheimer
1864 - 1915
•
•
Targeting Amyloid-Beta Protein (Aβ)
DAEFRHDSGYEVHHQKLVFFAEDVGSNKGAI IGLMVGGVVIA Aβ42
•
There are many specific receptors on microglia cells that target Ab for its
binding and phagocytosis.
• In AD and other amyloidogenic diseases the phagocytosis pathways of the
amyloids are damaged although other phagocytosis activities are unchanged.
• AIM 1:
To design and construct new biomaterial agents
that directly inhibit the aggregation and toxicity of
Ab.
Health conditions
Disease conditions
RESTING MICROGLIA
• AIM 2:
To enhance the clearance of Ab by targeting it to
microglia/macrophages through non-Abdependent mechanisms.
NEURONAL
DAMAGE
Ab clearance
Aβ clearance
Inflammation
and Apoptosis
Inflammation
Surface-Modified Protein Microspheres
Rahimipour, S. et al. Chem. - Eur. J., 2011, 17, 11171
Characterization of KLVFFMicrospheres
Number (%)
1.49 1.36
1 mm
Particle Diameter (mm)
KLVFF-Microspheres Reduce Ab Aggregation
and Ab-Induced Inflammation
80
*
TNFa (pg/ml)
70
60
**
50
40
30
20
10
0
al
s se A
B a le a
e
R
b 42
M
-C
-C
F
F
2
VF Ab 4 LVF
L
K +
K
M
B
SA
M
ic
.
Rahimipour S. et al. Biomacromolecules, 2013, 14, 110-6.
KLVFF-Microspheres Can be Used as a
Diagnostic Agents
Without GNP
KLVFF-CM with GNP
• The particles are not toxic to animals even after repeated i.v. injections
• The particles has long circulation time (~ 24 h) allowing efficient Ab binding
Other Applications:
Vascular imaging
Cancer targeted theranostics
Polydopamine as a Versatile Material for Generation of
Biocompatible Nanocapsules with Antibacterial and
Anticancer Activity
Novel nanomatrices and nanocapsules - NMP 6 – 2015 /
Nanomedicine therapy for cancer- NMP 11 – 2015:
Polydopamine as a Versatile Agent for Generation of Biocompatible
Nanocapsules with Antibacterial and Anticancer Activity
Cisplatin Coated Polydopamine Nanocapsules as
Potential Anticancer Agents
% Pt Released
70
45
20
-5
)
er
er
4.0
uff
uff )
b
b
H
M
te
)
te
(p
er ClO bona 24 m
eta 4.0
f
f
c
,
A (pH
r
a
bu
Ca H 8.6
te M N
a
t
m
p
e
(
Ac + 8
S
PB
Cisplatin Coated Polydopamine Nanocapsules as
Potential Anticancer Agents
100
O
H2 N
O
H 2N
O
O
O
1
N
H
N
N O
NO2
H
N
H
N
O
O
Events
H
N
O
O
HS
75
MRI
NO2
H
N
O
O
O
2
N
H
N
N O
50
25
0
1
10
100
1000
Fluorescence Intensity
PC3-viability
MCF7 viability
100
NS
NS-Pt
CP-DOPA
Pt (µg)
CP
NS
NS-pt
CP-DOPA
Pt (µg)
CP
control
0.24
0.49
0.98
1.95
3.90
control
0.24
0.49
0.98
1.95
3.90
0.24
0.49
0.98
1.95
3.90
0
4.20
8.41
16.82
25.23
0
25
0.24
0.49
0.98
1.95
3.90
25
50
4.20
8.41
16.82
25.23
50
75
10
20
30
% Viability
75
10
20
30
% Viability
100

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