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Grand Challenges for Nanomedicine and Nanobiology Workshop Houston, Texas August 27 th , 2007. Personal Thoughts. Targeted Delivery (Timing) EPR Tumor vasculature Potential for clinical impact versus clinical translation Diagnostics and Nanotechnology? Training and Team Science - PowerPoint PPT Presentation
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Grand Challenges for Nanomedicine
and Nanobiology Workshop
Houston, Texas
August 27th, 2007
Personal ThoughtsPersonal 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 SessionsUpcoming 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 OpportunitiesUpcoming 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 OpportunitiesUpcoming NCI Funding Opportunities
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
nano.cancer.gov
Nanotechnology Characterization Lab (NCL)Role and Updates Nanotechnology Characterization Lab (NCL)Role and Updates
The NCL developed and standardized analytical cascade that tests the pre-clinical toxicology, pharmacology, and efficacy of nanoparticles and devices.
Next submission date (9/1/2007 and 12/1/2007)
In VitroIn Vivo
Physicochemical
NCL in vivo Characterization AssaysNCL in vivo Characterization Assays
Initial disposition study• Tissue Distribution• Clearance• Half-life• Systemic exposure (plasma AUC)
Immunotoxicity• 28 day screen• Immunogenicity (repeat-dose tox
study)
Dose -Range Finding Toxicity• Blood Chemistry• Hematology• Histopathology• Gross Pathology
GLP Studies• PK/ADME• Expanded Single Dose Acute Tox
0
1
2
3
4
5
6
7
8
9
0 5 10 15 20 25 30 35 40 45 50
Time (hours)
% In
jec
ted
do
se
3 H /m
L 3H-Liposome3H-Ghost Liposome3H Labeled Carrier + Drug3H Labeled Carrier
0
1
2
3
4
5
6
7
8
9
0 5 10 15 20 25 30 35 40 45 50
Time (hours)
% In
jec
ted
do
se
3 H /m
L 3H-Liposome3H-Ghost Liposome3H Labeled Carrier + Drug3H Labeled Carrier
Plasma Profile
SEX
MALE
FEMALE
DOSE GROUP CONTROL + DRUG CONTROL +DRUG
NUMBER OF ANIMALS 3 3 3 3
BODY WEIGHT (gram)a 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
HEART
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
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
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 0.71+ 0.09 0.51 + 0.05* 0.42 + 0.10 0.57 + 0.15
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
LUNG Absolute Weight gram 1.72+ 0.50 1.45 + 0.14 1.30 + 0.18 1.33 + 0.10
Per Body Weight % 0.54+ 0.22 0.46 + 0.08 0.55 + 0.06 0.52 + 0.12
Per Brain Weight % 88+ 27 76.+ 11 71 + 7 80 + 14
Organ Weights Main Study
SEX
MALE
FEMALE
DOSE GROUP CONTROL +DRUG CONTROL +DRUG
NUMBER OF ANIMALS 3 3 3 3 Red Blood Cells
Hematocrit (Hct) % 46.60+1.
27 44.88+0.5
9 43.18+2.4
4 43.80+1.2
5 Hemoglobin Conc. (Hb)
g/dL 15.7+0.4 15.2+0.1 14.7+0.6 15.4+0.2
Mean Corp. Hb. (MCH)
pg 20.7+0.5 21.2+0.1 20.7+0.4 20.87+0.4
5 Mean Corp. Hb. Conc. (MCHC)
g/dL 33.73+0.
81 23.87+17.38
34.2+1.0 35.2+0.61
Mean Corp. Volume (MCV)
fL 61+2 63+1 60+2 59+3
Total Erythrocyte Count (RBC)
M/L
7.61+0.06
7.17+0.08*
7.13+0.41 7.39+0.15
Red Cell Distribution
Width % 18.0+0.5 16.3+0.6* 17.4+0.5 17+0.26
White Blood Cells
Lymphocytes 103/L
7.61+1.54
6.9+2.7 5.9+2.0 3.46+1.45
Macrophage/ Monocytes
103/L
0.23+0.19
0.57+0.68 0.33+0.17 0.10+0.10
Granulocytes 103/L
1.76+0.31
1.15+0.36 0.96+0.36 1.23+0.31
Total Leukocytes (WBC)
103/L
9.60+1.77
8.64+3.70 7.17+2.29 4.78+1.41
Clotting Potential Platelet Count
(PLT) 103/L
807+136 925+75 645+165 249+411
Mean Platelet Volume (MPV)
fL 8.1+0.2 7.6+0.4 7.67+0.84 7.83+0.40
Platelet Distribution
Width (PDW) % 34.1+1.2 34.5+1.6
34.07+2.97
34.13+0.70
Plateletcrit (PLT) % 0.66+0.1
1 0.7+0.03 0.49+0.14 0.75+0.13
Hematology Interim Study
Current NCL CollaboratorsCurrent NCL Collaborators
Onsite Program Contacts Onsite Program Contacts
Larry Nagahara, Ph.D.Nanotechnology Projects Manager
Email: [email protected]
Jerry Lee, Ph.D.
Tech. Dev. Program Officer
Email: [email protected]