grand challenges for nanomedicine and nanobiology workshop houston, texas august 27 th , 2007

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

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Time (hours)

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L 3H-Liposome3H-Ghost Liposome3H Labeled Carrier + Drug3H Labeled Carrier

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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:  nagaharl@mail.nih.gov

Jerry Lee, Ph.D.

Tech. Dev. Program Officer

Email: leejerry@mail.nih.gov