Transcript NCI Alliance for Nanotechnology in Cancer: Research

Grand Challenges for Nanomedicine
and Nanobiology Workshop
Houston, Texas
August 27th, 2007
Personal Thoughts
 Targeted Delivery (Timing)
• EPR
• Tumor vasculature
 Potential for clinical impact versus clinical
translation
 Diagnostics and Nanotechnology?
 Training and Team Science
• Multi-PI R01s
• NIH Pathway to Independence Award (K99/R00)
• Mentored Research Scientist Development Award
(K01)
• Mentored Clinical Scientist Development Award
(K08)
• Clinical Oncology Training Grants (K12)
Upcoming Sessions
Nano Tutorial Sessions: Oct 16th, 2007

Tutorial Session 1: Cells, Tissues, and Organs: Basic Principles of
Functional Histology and Pathology

Tutorial Session 2: Basic Cancer Biology

Tutorial Session 3: Animal Models

Tutorial Session 4: Biodistribution of Nanoparticles

Tutorial Session 5: Materials Science/Nanotechnology

Clinical Pathway
• Clinical trial grants and contracts
• FDA
• Nanotechnology Characterization Lab
ASCB Special Session: Dec 1st, 2007
Upcoming NIH Funding Opportunities
 Nanoscience and Nanotechnology in Biology and Medicine
(R01&R21), Oct. 22nd, 2007
 Biology of Breast Pre-Malignancies (R01), Nov. 17th, 2007
• RFA-CA-07-047
• insufficient understanding of normal and pre-cancer biology
Upcoming NCI Funding Opportunities

nano.cancer.gov
SBIR Solicitation (PHS-2008-1), Nov. 5th,
2007
•
Topic 241: Multifunctional Therapeutics Based
on Nanotechnology
•
Topic 252: Nanotechnology Imaging and
Sensing Platforms for Improved Diagnosis of
Cancer

Multidisciplinary Development and Training
in Cancer Nanotechnology Award (F32/F33),
TBA

Innovative Molecular Analysis Technologies
[IMAT] (R21/R33), Sept. 27th, 2007
•
Innovative Technologies for the Molecular
Analysis of Cancer: RFA-CA-07-033
• Application of Emerging Technologies for
Cancer Research: RFA-CA-07-035
Nanotechnology Characterization Lab (NCL)
Role and Updates
Physicochemical
 The NCL developed and
standardized analytical
cascade that tests the preclinical toxicology,
pharmacology, and efficacy
of nanoparticles and devices.
 Next submission date
(9/1/2007 and 12/1/2007)
In Vitro
In Vivo
NCL in vivo Characterization Assays
Plasma Profile
9
Tissue Distribution
Clearance
Half-life
Systemic exposure (plasma AUC)
5
4
3
2
1
0
0
5
10
15
20
28 day screen
Immunogenicity (repeat-dose tox
study)
Dose -Range Finding Toxicity
•
•
•
•
Blood Chemistry
Hematology
Histopathology
Gross Pathology
Organ Weights Main Study
SEX
FEMALE
MALE
CONTROL
NUMBER OF ANIMALS
3
BODY WEIGHT (gram)a
+ DRUG
CONTROL
+DRUG
3
3
3
330+ 53
321 + 73
237 + 31
271 + 81
BRAIN
Absolute Weight
gram
1.95+ 0.10
1.94 + 0.05
1.83 + 0.10
1.93 + 0.24
Per Body Weight
%
0.60+ 0.07
0.56 + 0.04
0.87 + 0.00
0.89 + 0.09
Absolute Weight
gram
1.30+ 0.21
1.08 + 0.19
0.94 + 0.19
0.89 + 0.09
Per Body Weight
%
0.41+ 0.09
0.34 + 0.03
0.39 + 0.05
0.34 + 0.06
Per Brain Weight
%
68.32+ 11.42
56.55 + 8.79
51.02 + 8.31
53.67 + 12.42
HEART
KIDNEYS
Absolute Weight
gram
2.96+ 0.47
2.18 + 0.65
1.66 + 0.21
1.83 + 0.47
Per Body Weight
%
0.90+ 0.11
0.68 + 0.08*
0.70 + 0.04
0.68 + 0.04
Per Brain Weight
%
152+ 24
114 + 28
90 + 7
113 + 44
LIVER
GLP Studies
•
•
PK/ADME
Expanded Single Dose Acute Tox
25
30
35
40
45
50
Time (hours)
DOSE GROUP

6
Immunotoxicity
•
•

3H-Liposome
3H Labeled Carrier + Drug
3H Labeled
Carrier
3H-Ghost
Liposome
7
3
Initial disposition study
•
•
•
•

% Injected dose H /mL

8
Absolute Weight
gram
16.05+ 2.58
12.61 + 3.07
8.11 + 1.36
10.99 + 3.02
Per Body Weight
%
4.94+ 1.08
3.93 + 0.25
3.41 + 0.17
4.08 + 0.10*
Per Brain Weight
%
825+ 141
661 + 139
441 + 48
676 + 279
SPLEEN
Absolute Weight
gram
Per Body Weight
%
0.22+ 0.04
0.16 + 0.04
0.18 + 0.02
0.21 + 0.01*
Per Brain Weight
%
36.46+ 5.12
27.01 + 4.66
22.97 + 3.90
35.01 + 14.19
Absolute Weight
gram
1.72+ 0.50
1.45 + 0.14
1.30 + 0.18
1.33 + 0.10
Per Body Weight
Per Brain Weight
%
%
0.54+ 0.22
0.46 + 0.08
0.55 + 0.06
0.52 + 0.12
88+ 27
76.+ 11
71 + 7
80 + 14
0.71+ 0.09
0.51 + 0.05*
0.42 + 0.10
0.57 + 0.15
LUNG
Hematology Interim Study
SEX
FEMALE
MALE
DOSE GROUP
CONTROL
+DRUG
CONTROL
NUMBER OF ANIMALS
Red Blood Cells
3
3
3
3
46.60+1.
27
44.88+0.5
9
43.18+2.4
4
43.80+1.2
5
15.7+0.4
15.2+0.1
14.7+0.6
15.4+0.2
20.7+0.5
21.2+0.1
20.7+0.4
20.87+0.4
5
33.73+0.
81
23.87+17.38
34.2+1.0
35.2+0.61
Hematocrit (Hct)
%
Hemoglobin
g/dL
Conc. (Hb)
Mean Corp. Hb.
pg
(MCH)
Mean Corp. Hb.
g/dL
Conc. (MCHC)
Mean Corp.
fL
Volume (MCV)
Total Erythrocyte
M/
Count (RBC)
L
Red Cell
Distribution
%
Width
White Blood Cells
3
10 /
Lymphocytes
L
3
10 /
Macrophage/
Monocytes
L
3
10 /
Granulocytes
L
3
10 /
Total Leukocytes
(WBC)
L
Clotting Potential
3
10 /
Platelet Count
(PLT)
L
Mean Platelet
fL
Volume (MPV)
Platelet
Distribution
%
Width (PDW)
Plateletcrit (PLT)
%
+DRUG
61+2
63+1
60+2
59+3
7.61+0.0
6
7.17+0.08
*
7.13+0.41
7.39+0.15
18.0+0.5
16.3+0.6*
17.4+0.5
17+0.26
7.61+1.5
4
0.23+0.1
9
1.76+0.3
1
9.60+1.7
7
6.9+2.7
5.9+2.0
3.46+1.45
0.57+0.68
0.33+0.17
0.10+0.10
1.15+0.36
0.96+0.36
1.23+0.31
8.64+3.70
7.17+2.29
4.78+1.41
807+136
925+75
645+165
249+411
8.1+0.2
7.6+0.4
7.67+0.84
7.83+0.40
34.1+1.2
34.5+1.6
34.07+2.9
7
34.13+0.7
0
0.66+0.1
1
0.7+0.03
0.49+0.14
0.75+0.13
Current NCL Collaborators
Onsite Program Contacts
 Larry Nagahara, Ph.D.
Nanotechnology Projects Manager
 Email: [email protected]
 Jerry Lee, Ph.D.
 Tech. Dev. Program Officer
 Email: [email protected]