# US 8,785,505 B2 · Toxicology and cellular effect of manufactured nanomaterials

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- Number: US 8,785,505 B2
- Document ID: US8785505B2
- Status: Granted
- Kind: B2
- Application number: 12/111,026
- Filed: 2008-04-28
- Published: 2009-10-29
- Granted: 2014-07-22
- Earliest claimed: 2005-10-28
- Assignees: The Regents of the University of California
- Applicants: Fanqing Chen
- Inventors: Fanqing Chen
- Web page: https://patentgrep.com/patent/US8785505B2

## CPC

- C12Q 1/6883: for diseases caused by alterations of genetic material
- A61K 47/6855: {the tumour determinant being from breast cancer cell}
- A61K 47/6925: {the form being a microcapsule, nanocapsule, microbubble or nanobubble}
- B82Y 5/00: Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
- G01N 33/5014: {for testing toxicity}
- C12Q 2600/106: Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
- C12Q 2600/142: Toxicological screening, e.g. expression profiles which identify toxicity
- C12Q 2600/158: Expression markers
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- B82Y: SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The increasing use of nanotechnology in consumer products and medical applications underlies the importance of understanding its potential toxic effects to people and the environment. Herein are described methods and assays to predict and evaluate the cellular effects of nanomaterial exposure. Exposing cells to nanomaterials at cytotoxic doses induces cell cycle arrest and increases apoptosis/necrosis, activates genes involved in cellular transport, metabolism, cell cycle regulation, and stress response. Certain nanomaterials induce genes indicative of a strong immune and inflammatory response within skin fibroblasts. Furthermore, the described multiwall carbon nanoonions (MWCNOs) can be used as a therapeutic in the treatment of cancer due to its cytotoxicity.

## Claims

### Claim 1

A composition, comprising: a multiwall carbon nanoonion having a diameter from 10-50 nm, wherein said nanoonion is conjugated to a tumor-targeting antibody and a magnetic resonance imaging reagent, further comprising an immunoliposome bound to or encapsulating the multiwall carbon nanoonion wherein said immunoliposome comprises a lipid comprised of phosphatidylethanolamine and/or phosphatidylcholine.

### Claim 2 (depends on 1)

The composition of claim 1 wherein the multiwall carbon nanoonion has a diameter of about 30 nm.

### Claim 3 (depends on 1)

The composition of claim 1 wherein the tumor-targeting antibody is a monoclonal antibody.

### Claim 4 (depends on 3)

The composition of claim 3 wherein the monoclonal antibody is specific for Erbβ2.

### Claim 5 (depends on 1)

The composition of claim 1 wherein the magnetic resonance imaging reagent is Gd-DPTA, 19F, 1H, or 125I.

### Claim 6 (depends on 1)

The composition of claim 1, wherein the immunoliposomes comprise disteroyl phosphatidylcholine/cholesterol (DSPC/Chol, 3:2 molar ratio) and PEG2000-derivatized disteroyl phosphatidylehtanolamine (PEG-PE), and wherein the tumor-targeting antibody comprises anti-HER2 MAb fragments.

### Claim 7 (depends on 1)

A method of treating cancer comprising delivering the composition of claim 1 to a subject in an effective therapeutic amount.

### Claim 8 (depends on 7)

The method of claim 7, wherein the effective therapeutic amount does not induce greater than 25% overexpression or underexpression of a gene following treatment.
