The development of nanotechnologies for nanomedical applications has become a

priority of the National Institutes of Health (NIH). Between 2! and 2"# the NIH
established a networ$ of eight Nanomedicine %evelopment &enters# as part of the
NIH Nanomedicine 'oadmap Initiative. In 2(# The National &ancer
Institute (N&I) committed )!!.* million over ( years for its +,lliance for
Nanotechnology in &ancer- program which funds seven &entres of ./cellence for
&ancer Nanotechnology (0im# 21). The funding supports various research pro2ects
in areas of diagnostics# devices# biosensors# micro3uidics and therapeutics.
,mong the long term ob2ectives of the NIH initiative are goals such as being able to
use nanoparticles to see$ out cancer cells before tumors grow# remove and4 or
replace +bro$en- parts of cells or cell mechanisms with miniature# molecular5si6ed
biological +machines-# and use similar +machines- as pumps or robots to deliver
medicines when and where needed within the body. ,ll of these ideas are feasible
based on present technology. However# we don7t $now enough about the physical
properties of intracellular structures and interactions between cells and
nanoparticles# to currently reach all of these ob2ectives. The primary goal of the NIH
is to add to current $nowledge of these interactions and cellular mechanisms# such
that precisely5built nanoparticles can be integrated without adverse side5e8ects.
9any di8erent types of nanoparticles currently being studied for applications in
nanomedicine. They can be carbon5based s$eletal5type structures# such as
the fullerenes# or micelle5li$e# lipid5based liposomes# which are already in use for
numerous applications in drug delivery and the cosmetic industry. &olloids# typically
liposome nanoparticles# selected for their solubility and suspension properties are
used in cosmetics# creams# protective coatings and stain5resistant clothing. :ther
e/amples of carbon5based nanoparticles are chitosan and alginate5based
nanoparticles described in the literature for oral delivery of proteins# and various
polymers under study for insulin delivery.
,dditional nanoparticles can be made from metals and other inorganic materials#
such as phosphates. Nanoparticle contrast agents are compounds that enhance 9'I
and ultrasound results in biomedical applications of in vivo imaging. These particles
typically contain metals whose properties are dramatically altered at the nano5
scale. ;old +nanoshells- are useful in the <ght against cancer# particularly soft5
tissue tumors# because of their ability to absorb radiation at certain wavelengths.
:nce the nanoshells enter tumor cells and radiation treatment is applied# they
absorb the energy and heat up enough to $ill the cancer cells. =ositively5charged
silver nanoparticles adsorb onto single5stranded %N, and are used for its detection.
9any other tools and devices for in vivo imaging (3uorescence detection systems)#
and to improve contrast in ultrasound and 9'I images# are being developed.
There are numerous e/amples of disease5<ghting strategies in the literature# using
nanoparticles. :ften# particularly in the case of cancer therapies# drug delivery
properties are combined with imaging technologies# so that cancer cells can be
visually located while undergoing treatment. The predominant strategy is to target
speci<c cells by lin$ing antigens or other biosensors (e.g. 'N, strands) to the
surface of the nanoparticles that detect speciali6ed properties of the cell walls. :nce
the target cell has been identi<ed# the nanoparticles will adhere to the cell surface#
or enter the cell# via a specially designed mechanism# and deliver its payload.
:ne the drug is delivered# if the nanoparticle is also an imaging agent# doctors can
follow its progress and the distribution of the cancer cell is $nown. >uch speci<c
targeting and detection will aid in treating late5phase metastasi6ed cancers and
hard5to5reach tumors and give indications of the spread of those and other
diseases. It also prolongs the life of certain drugs that have been found to last
longer inside a nanoparticle than when the tumor was directly in2ected# since often
drugs that have been in2ected into a tumor di8use away before e8ectively $illing
the tumor cells.
, signi<cant development in the treatment of cancer was the pairing of si'N, (small
interfering 'N,) treatments with nanoparticle delivery. In )???# si'N, was <rst
described as a novel means of inhibiting protein e/pression in cells. However# the
'N, strands were often destroyed by cellular mechanisms before reaching their
targets. Nanoparticles provide the protection and delivery mechanisms si'N,
molecules need to reach target tissues. >everal companies have already entered
clinical trials of nanoparticles5delivered si'N, therapies (,lper 2").
9olecular self5assembly is the phenomenon through which molecules assemble
spontaneously into de<ned# stable formations based on atomic interactions such as
hydrogen bonding# hydrophobic and van der @aals forces. +Bottom5up- construction
of nanoparticles ta$es advantage of molecular self5assembly to build speci<c
structures based on our understanding of these spontaneous formations. :ne
application of this is to use the speci<city of @atson5&ric$ %N, base pairing to build
nucleic acids of de<ned structures with particular uses. In another novel application
of molecular self5assembly# under development in >wit6erland# pore proteins are
introduced into nanoparticles during polymer assembly. The pores are incorporated
into the surface matri/# and their opening and closing allow drug delivery speci<c to
certain environmental conditions (in this case pH changes) in the cell (Bro6 et al.
2"). =ores often open or close as they react to pH# temperature or other
environmental factors. Ase of similar pores in nanoparticles allows speci<c delivery
or biosensing under speci<c cellular conditions# for e/ample# insulin delivery when
blood sugar levels indicate a need.
Bollowing payload delivery# it is often desirable for the nanoparticles to somehow be
removed or metaboli6ed# ideally without any to/ic side e8ects. Indeed# the
advantages to using nanoparticles are that to/ic side e8ects of traditional radiation
and chemotherapies can be avoided# by treating only the tumor# or unhealthy# cells
and not damaging nearby healthy tissue. >ome nanoparticles are e/pected to be
relatively safe because of their propensity to dissolve once inside cells# and some
consist of materials that are already in use in biomedicine# such as nanoparticles
made from the same polymers as are used for sutures (Bullis# 2"). @hatever the
approach# the bene<ts of nanoparticle delivery are enormous and include improved
bioavailability of drugs by targeting speci<c organs# tissues or tumors# thereby
providing the highest dose of drug directly where it is needed# and reducing waste
and costs due to brea$down prior to a drug meeting its target.
Nanomedicine is a relatively new area of biotechnology# but the possibilities for new
therapies and surgeries to treat illnesses and diseases such as cancer# seem
endless. The concept of nanorobots and cell repair machines is also viable and may
some day be as commonplace as ta$ing an asprin is today.
9edical applications of molecular nanotechnology
9olecular nanotechnology is a speculative sub<eld of nanotechnology regarding the
possibility of engineering molecular assemblers# machines which could re5order
matter at a molecular or atomic scale. 9olecular nanotechnology is highly
theoretical# see$ing to anticipate what inventions nanotechnology might yield and
to propose an agenda for future inCuiry. The proposed elements of molecular
nanotechnology# such as molecular assemblers and nanorobots are far beyond
current capabilities.
Nanorobots
The somewhat speculative claims about the possibility of using nanorobots
D)"E
in
medicine# advocates say# would totally change the world of medicine once it is
reali6ed. Nanomedicine
D)ED)(E
would ma$e use of these nanorobots
(e.g.# &omputational ;enes)# introduced into the body# to repair or detect damages
and infections. ,ccording to 'obert Breitasof the Institute for 9olecular
9anufacturing# a typical blood borne medical nanorobot would be between .(5*
micrometres in si6e# because that is the ma/imum si6e possible due
tocapillary passage reCuirement. &arbon could be the primary element used to build
these nanorobots due to the inherent strength and other characteristics of some
forms of carbon (diamond4fullerene composites)# and nanorobots would be
fabricated in des$top nanofactories
D)1E
speciali6ed for this purpose.
Nanodevices could be observed at wor$ inside the body using 9'I# especially if their
components were manufactured using mostly
)*
& atoms rather than the natural
)2
&
isotope of carbon# since
)*
& has a non6ero nuclear magnetic moment. 9edical
nanodevices would <rst be in2ected into a human body# and would then go to wor$
in a speci<c organ or tissue mass. The doctor will monitor the progress# and ma$e
certain that the nanodevices have gotten to the correct target treatment region.
The doctor will also be able to scan a section of the body# and actually see the
nanodevices congregated neatly around their target (a tumor mass# etc.) so that he
or she can be sure that the procedure was successful.
Cell repair machines
Asing drugs and surgery# doctors can only encourage tissues to repair themselves.
@ith molecular machines# there will be more direct repairs.
D)FE
&ell repair will utili6e
the same tas$s that living systems already prove possible. ,ccess to cells is
possible because biologists can stic$ needles into cells without $illing them. Thus#
molecular machines are capable of entering the cell. ,lso# all speci<c biochemical
interactions show that molecular systems can recogni6e other molecules by touch#
build or rebuild every molecule in a cell# and can disassemble damaged molecules.
Binally# cells that replicate prove that molecular systems can assemble every
system found in a cell. Therefore# since nature has demonstrated the basic
operations needed to perform molecular5level cell repair# in the future#
nanomachine based systems will be built that are able to enter cells# sense
di8erences from healthy ones and ma$e modi<cations to the structure.
The healthcare possibilities of these cell repair machines are impressive.
&omparable to the si6e of viruses or bacteria# their compact parts would allow them
to be more comple/. The early machines will be speciali6ed. ,s they open and close
cell membranes or travel through tissue and enter cells and viruses# machines will
only be able to correct a single molecular disorder li$e %N, damage or en6yme
de<ciency. Gater# cell repair machines will be programmed with more abilities with
the help of advanced ,I systems.
Nanocomputers will be needed to guide these machines. These computers will
direct machines to e/amine# ta$e apart# and rebuild damaged molecular structures.
'epair machines will be able to repair whole cells by wor$ing structure by structure.
Then by wor$ing cell by cell and tissue by tissue# whole organs can be repaired.
Binally# by wor$ing organ by organ# health is restored to the body. &ells damaged to
the point of inactivity can be repaired because of the ability of molecular machines
to build cells from scratch. Therefore# cell repair machines will free medicine from
reliance on self repair alone.
Nanonephrology
Nanonephrology is a branch of nanomedicine and nanotechnology that deals with ))
the study of $idney protein structures at the atomic levelH 2) nano5imaging
approaches to study cellular processes in $idney cellsH and *) nano medical
treatments that utili6e nanoparticles and to treat various $idney diseases. The
creation and use of materials and devices at the molecular and atomic levels that
can be used for the diagnosis and therapy of renal diseases is also a part of
Nanonephrology that will play a role in the management of patients with $idney
disease in the future. ,dvances in Nanonephrology will be based on discoveries in
the above areas that can provide nano5scale information on the cellular molecular
machinery involved in normal $idney processes and in pathological states. By
understanding the physical and chemical properties of proteins and other
macromolecules at the atomic level in various cells in the $idney# novel therapeutic
approaches can be designed to combat ma2or renal diseases. The nano5scale
arti<cial $idney is a goal that many physicians dream of. Nano5scale engineering
advances will permit programmable and controllable nano5scale robots to e/ecute
curative and reconstructive procedures in the human $idney at the cellular and
molecular levels. %esigning nanostructures compatible with the $idney cells and
that can safely operate in vivo is also a future goal. The ability to direct events in a
controlled fashion at the cellular nano5level has the potential of signi<cantly
improving the lives of patients with $idney diseases