Tài liệu Nanotechnology in Cancer Treatment and Detection doc

Scale and Scope The nanoparticles discussed in this presentation are typically between 20-150 nm or roughly 100 times smaller than most human cells Cancer Nanotechnology research i

Nanotechnology in Cancer Treatment and Detection

Richard Acosta

Motivation

• Ineffectiveness of many Cancer treatments

• Numerous side effects

• Difficulties in early Cancer detection

• No immunization

Scale and Scope

The nanoparticles discussed in

this presentation are typically

between 20-150 nm or roughly

100 times smaller than most

human cells

Cancer Nanotechnology research

is interdisciplinary and

incorporates Biology, Chemistry,

Engineering, Medicine, and

Physics

Properties of Cancer Cells

• Epidermal Growth Factor Receptor (EGFR)

over expression and over activity

have been associated many different

types of Cancer

• Cancer cells have a unique properties that can be exploited by nanoparticles

• Their rapid rate of growth causes them to intake an abnormal amount of

nutrients (i.e., folic acid)

• Nanoparticles can be used to target bio-markers or antigens that are

highly specific to Cancer cells

• 99% of chemotherapy drugs do not reach the

Cancer cells

• Nanotubes, nanorods, dendrimers,

nanospheres, nanoantennas, … using

carbon, iron, gadolinium, gold, silicon, etc

• Antigen binding peptide ligands are attached

to the nanostructures

• Folic acid baiting

• Passive targeting - Leaky blood vessels near

tumors cause the nanoparticles to cluster

around the tumors

Nanoparticle Specialization

Uses in Treatment

Intracellular Drug Delivery

The Trojan Horse

Cytotoxic chemical payload

Methotrexate, Docetaxel, etc…

Uses in Treatment

Experiment on mice bearing

human prostate tumors

After approximately 3 months

100% of the mice treated with the

targeted nanoparticles survived

57% of the mice treated with

untargeted nanoparticles survived

14% of the mice with Docetaxel

alone survived

Amount of weight loss and white

blood cell count confirmed far lower

toxicity for the targeted nanoparticles

Comparative efficacy study in LNCaP s.c xenograft nude mouse model of PCa

Farokhzad O C et.al PNAS 2006;103:6315-6320

©2006 by National Academy of Sciences

Uses in Treatment

Photothermal Ablation

Cancer cells die at 42° C (108° F), normal cells die at about 46° C (115° F)

Current optical fiber treatment

Hollow, gold nanospheres are 50 times more effective at absorbing light near the infrared than solid gold nanoparticles

Nanoparticles can be tuned to be excited only by certain ranges of light

Uses in Treatment

In another study, pre-clinical trials reveal that a single intravenous nanoparticle injection eradicated 100 percent of tumors in mice when exposed to

near-infrared light

Most work is being done with near-infrared light, which is harmless to humans but can only penetrate human tissue about 1.5 inches Nanoparticles heated up

to 70° C (160° F)

The Kanzius RF Machine uses radio waves for dielectric heating

Uses in Detection

Gold nanoparticles in this image showed 600 percent more affinity to Cancer cells than healthy cells (EGFR binding)

White light and simple, inexpensive microscope is all that’s necessary for

powerful ex vivo Cancer detection

The scattering is so strong that even one nanoparticle can be detected

Uses in Detection

Using a metal-organic framework with metals such as gadolinium or iron, nanoparticles can be used as MRI contrast agents

For the same amount of contrast, only 1/3 of the contrast agent is necessary using nanoparticle targeting

Uses in Detection

Fluorescent Microscopy

Nanoparticles can serve as dual detection devices for both magnetic resonance and microscopy

Current Limitations

Cancer targeting is highly dependent on surface chemistry Not just any nanoparticle will work

The need for biocompatible and stable nanoparticles

Side-effects and toxicity

Environmental impact

Uncharted territory

Future

Human clinical trials within the next 2-3 years

Highly specific team of communicating multifunctional nanoparticles used

in the discovery, treatment, and prevention of Cancer growth

Safer, more consistent, and highly specific nanoparticle production

Turning Cancer into a chronic, but manageable disease within the next 15-20 years

Summary

-Different types of Cancer cells have unique properties that can be

exploited by nanoparticles to target the Cancer cells

-Nanoparticles can be used to detect/monitor (by utilizing or adding optic, magnetic, and fluorescent properties) and to treat Cancer (by Heat ablation, chemotherapy, gene therapy)

-No human trials have been performed yet and human trials are still at

least a few years away (Unknown side effects, toxicity, difficulty in

manufacturing and harmful byproducts, need for highly specific

nanoparticles)

Sources

Applications ScienceDaily Retrieved May 24, 2009, from http://www.sciencedaily.com- /releases/2009/03/090322154415.htm

Burning Of Melanoma ScienceDaily Retrieved May 24, 2009,

from http://www.sciencedaily.com- /releases/2009/02/090202074856.htm

Research 2006; 23(7): 1417-50

detecting and treating cancer Drug Development Research 2006; 67: 70-93

Biochemistry 2006; 97: 1184-90

Nanoparticles Used as Multifunctional Nanomedicines for the Targeted Imaging and Treatment of Cancer

Biomacromolecules 2009 10 (4), 983-993

Simultaneous Targeting, Dual-Mode Imaging, and Photothermal Ablation of Cancer Cells Angewandte

Chemie International Edition (2009)

threshold average temperature for cell death in an in vitro retinal model using thermograph Proc SPIE 7175,

71750G (2009), DOI:10.1117/12.807861

before print April 10, 2006, doi:10.1073/pnas.0601755103

Questions

1)  Which of the following are not potential methods for treating Cancer

using nanotechnology

a)  Photothermal ablation

b)  Folic acid introduction

c)  Cytotoxic drug delivery

d)  Gene therapy

e)  None of the above

2) A cause for the stall in utilizing nanotechnology treatment on a mass scale is a)  Unknown toxic effects of nanoparticles

b)  Environmental repercussions

c)  Lack of human clinical trials

d)  Inefficient nanoparticle creation techniques

e)  All of the above