only l1: introduction to nanomedicine use course 207 243 ...nano.ucsd.edu/~l7zhang/teaching/lecture...

L1: Introduction to Nanomedicine

April 3, 2018

NANO 243/CENG 207 Course Use Only

Evolution of Humankind and Disease

~ 2 million years

“The history of disease is vastly older than that of humankind itself.

Indeed, disease and parasitism have been inseparable companions to

life since the dawn of life on Earth.” by Robert A. Freitas, Jr.


Found from Fossils (Archaeologists and Anatomists)

5 million years ago: Bacteria similar to those responsible for many

infections that afflict people today

1.75 million years ago: Body chemistry disorders due to malnutrition

0.5 million years ago: Bone cancer had a morbid growth on a Java

man’s femur

75000 years ago: Clear evidence of arthritis, tooth loss, and

suppurative bone disease


Nowadays: Too Many Diseases to List

Latest Data from NCHS:

• Number of deaths: 2,352,512

• Death rate: 733.1 deaths per 100,000 population

• Number of deaths for leading causes of death:•

• Heart disease: 537,397

• Cancer: 510,191

• Chronic lower respiratory diseases: 142,430

• Stroke (cerebrovascular diseases): 128,603

• Alzheimer's disease: 78,889

• Diabetes: 68,504

• Influenza/Pneumonia: 53,582

• Nephritis, nephrotic syndrome, and nephrosis: 48,714

• Septicemia: 35,587


The History of Scientific Medicine

Religious

Empirical Natural

Empirical Religious

Authoritative Observational

EmpiricalRational

ScientificMolecular

ScientificNanomedicine

3000

BC

500

BC

400

AD

1500

AD

1850

AD

1940

AD

2010

AD

Cecil Textbook of Medicine, 1992NANO 243/CENG 207 Course Use Only

Definition of Nanomedicine

Nanomedicine: A branch of medicine concerns with the

application of nanotechnology to the prevention and treatment of

disease. It involves the monitoring, repair, construction, and

control of human biological systems at the molecular level, using

engineered nanodevices and nanostructure.

(Freitas Jr., Nanomedicine, vol 1, 1999)

Nanotechnology is the understanding and control of matter at

dimensions between approximately 1~100 nm, where unique

phenomena enable novel applications. Encompassing nanoscale

science, engineering, and technology, nanotechnology involves

imaging, measuring, modeling, and manipulating matter at this

length scale.

(National Nanotechnology Initiative)NANO 243/CENG 207 Course Use Only

Length Scale of Nanomedicine

At nanometer scale, materials have unique physical and chemical properties, such as ultra

small size, large surface area to mass ratio, and high reactivity, which are different from bulk

materials of the same composition.

These properties can be used to overcome some of the limitations found in traditional

therapeutic and diagnostic agents.


History of Nanomedicine

1959, Richard Feynman “Although it is a very wild idea, it would be interesting in

surgery if you could swallow the surgeon. You put the

mechanical surgeon inside the blood vessel and it goes

into the heart and looks around. It finds out which valve is

the faulty one and takes a little knife and slices it out. Other

small machines might be permanently incorporated in the

body to assist some inadequately functioning organ.”

First known proposal for

nanomedical procedure

to treat heart disease

1983, Eric Drexler

First technical paper on

“Cell Repair Machines”

Invited by an editor of the Journal of American Medical

Association, but was dismissed by a referee as “science

fiction”.

1966, Isaac Asimov

“Fantastic Voyage”



1990s, • Biocompatible materials and analytical techniques

• Surgical and dental practice

• Nerve cell research using intracellular electrodes

• Biostructures research and biomolecular research using

near-field optical microscopy, scanning probe microscopy

and optical tweezers

• Vaccine design

Nanoscale materials

technology has found

wide use in medicine



More recently,

Various nanomedicine

products are used in

the clinic and the list is

growing…

Clin. Pharm. Ther., 2008, 83, 761


Categories of Nanomedicine

Biomaterial

Immunotherapy

Active ImplantDiagnosis & Imaging

Nanomedicine

Drug Delivery

Detoxification


Prolong drug systemic circulation half-life

Targeted delivery to reduce harmful side effects

Sustained and controlled drug release

Facilitate administration by improving drug solubility

Improve patient compliance due to less invasive dosing

Nanomedicine: Drug Delivery

Drug Delivery: Nanoscale particles/molecules developed to improve the

bioavailability, pharmacokinetics and efficacy of therapeutics.


The application of nanotechnology to drug delivery has already had a significant impact

on many areas of medicine. Numerous nanoparticle platforms are currently under various

stages of preclinical and clinical development.

Nanomedicine: Drug Delivery

Nanoparticle

cores

Platelets

Platelet membrane-

cloaked nanoparticles

(PNP)

Subendothelium binding

Pathogen binding

Immunocompatibility

Macrophage

S. aureus

Damaged

vasculature

Nature 2015, 526, 118

Here we report on the

preparation of polymeric

nanoparticles enclosed in the

plasma membrane of human

platelets, which are a unique

population of cellular

fragments that adhere to a

variety of disease-relevant

substratesNANO 243/CENG 207 Course Use Only

Detoxification: Nanoscale particles/molecules developed to absorb, deactivate or

neutralize harmful compounds in our body.

Nanomedicine: Detoxification

Nature Nanotechnology 2013, 8, 187

Two or more enzymes with

complementary functions can be

assembled and encapsulated within a

thin polymer shell to form enzyme

nanocomplexes. These nanocomplexes

exhibit improved catalytic efficiency and

enhanced stability when compared with

free enzymes. Furthermore, the co-

localized enzymes display

complementary functions, whereby

toxic intermediates generated by one

enzyme can be promptly eliminated by

another enzyme. It was shown that

nanocomplexes containing alcohol

oxidase and catalase could reduce

blood alcohol levels in intoxicated mice,

offering an alternative antidote and

prophylactic for alcohol intoxication.


Immunotherapy: Using nanotechnology to leverage, manipulate, and/or supplement

endogenous immunity to better prevent or treat different diseases.

Nanomedicine: Immunotherapy

Nature 2016, 534, 396

a. This paper describes a nanoparticulate RNA vaccine formulated to preferentially target dendritic cells

(DCs) when administered intravenously. Nanoparticle uptake by precursor dendritic cells causes them to

develop into mature antigen-presenting dendritic cells that migrate to the T cells. Uptake of nanoparticles by

plasmacytoid dendritic cells promotes secretion of an initial wave of interferon protein that helps to prime the

first steps of T-cell activation. b, Translating the RNA within the nanoparticles, the mature dendritic cells

express tumour antigens and present them to the T cells. Nanoparticle uptake by macrophages leads to a

second wave of interferon release, which fully primes the T cells against specific antigens. c, The primed T

cells then attack tumour cells.


Nanomedicine: Imaging

In Vivo Imaging: Nanoparticle contrast agents, particularly for MRI, ultrasound,

and flourecence that provide improved contrast and favorable biodistribution.

Nerve preservation is an

important goal during surgery

because accidental transection

or injury leads to significant

morbidity, including numbness,

pain, weakness or paralysis.

Nerves are usually identified by

their appearance and relationship

to nearby structures or detected

by local electrical stimulation

(electromyography), but thin or

buried nerves are sometimes

overlooked.

NP41 can highlight buried nerve branches invisible by

standard illumination

Nature Biotechnology 2011, 29, 352


Nanomedicine: Active Implant

Active Implants: Particles/materials that improve the surfaces and biocompatibility of

device housings.

Nature Biotechnology 2016, 34, 345

(a) Phase contrast imaging of spheres retrieved after 4 weeks in the intraperitoneal space show less fibrosis on Z2-Y12, Z1-Y15 and Z1-Y19 spheres than on SLG20.

(b) Confocal imaging of retrieved spheres from a after 4 weeks in the intraperitoneal space show significantly less macrophage (CD68, CD11b), myofibroblast (SMA) and general cellular deposition (DAPI) on Z2-Y12 spheres.

The foreign body response is an immune-mediated reaction that can lead to the failure of implanted medical

devices and discomfort for the recipient. There is a critical need for biomaterials that overcome this key

challenge in the development of medical devices. Here a combinatorial approach for covalent chemical

modification is used to generate a large library of variants of one of the most widely used hydrogel

biomaterials, alginate.


Nanomedicine: Biomaterial

Biomaterials: Self-assembling particles or other types of nanomaterial that

improve the mechanical properties and the biocompatibility of biomaterials for

medical implants. Examples include nanocomposite materials used as dental

fillers and nanohydroxyapatite used for implant coatings and bone substitutes.

Also decoration of implant materials with biologically active signal molecules that

stimulate, for example, cell growth or differentiation.

Angew. Chem. Int. Ed. 2012, 51, 2602

A smart polymer surface has two

reversibly switchable equilibrium

states, a cationic N,N-dimethyl-2-

morpholinone (CB-Ring) and a

zwitterionic carboxy betaine (CB-

OH). CB-Ring will kill bacteria

upon contact under dry

conditions, whereas CB-OH will

release the previously attached

and dead bacteria and further

resist adhesion of bacteria under

wet conditions.NANO 243/CENG 207 Course Use Only

Nanomedicine: An Interdisciplinary Subject

Nanomedicine Chemical

Engineering

Nanoengineering

Physics

Pharmacy

Medicine

Chemistry

Bioengineering

Materials

Science


Drug Delivery

Biomaterial

Immunotherapy

Active ImplantDiagnosis & Imaging

Nanomedicine

Drug Delivery

Detoxification

This course will focus on drug delivery, including both

fundamental engineering principles and cutting-edge applications.


only l1: introduction to nanomedicine use course 207 243 ...nano.ucsd.edu/~l7zhang/teaching/lecture...

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