nanomedicine is the medical application of nanotechnology.doc
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Nanomedicine is the medical application ofnanotechnology.[1] Nanomedicine rangesfrom the medical applications ofnanomaterials, tonanoelectronicbiosensors, andeven possible future applications ofmolecular nanotechnology. Current problems fornanomedicine involve understanding the issues related totoxicityandenvironmentalimpact ofnanoscale materials. One nanometer is one-millionth of a millimeter.
Nanomedicine research is receiving funding from the USNational Institutes ofHealth. Of note is the funding in 2005 of a five-year plan to set up four nanomedicinecenters. In April 2006, the journalNature Materials estimated that 130 nanotech-
based drugs and delivery systems were being developed worldwide. [2]
Contents
[hide] 1 Overview
2 Medical use of nanomaterialso 2.1 Drug delivery
2.1.1 Applications and reported research studieso 2.2 Protein and peptide delivery
2.2.1 Applications and reported research studieso 2.3 Cancer
o 2.4 Surgery
o 2.5 Visualization
o 2.6 Tissue engineering
o 2.7 Antibiotic resistance
o 2.8 Immune response
3 Diagnostic and medical devices
4 Neuro-electronic interfaces
5 Medical applications of molecular nanotechnology
o 5.1 Nanorobots
o 5.2 Cell repair machines
o 5.3 Nanonephrology
6 See also
7 References
8 External links
[edit] Overview
The biological and medical research communities have exploited the uniqueproperties of nanomaterials for various applications (e.g., contrast agents for cellimaging and therapeutics for treating cancer). Terms such as biomedicalnanotechnology, nanobiotechnology, and nanomedicine are used to describe thishybrid field. Functionalities can be added to nanomaterials by interfacing them with
biological molecules or structures. The size of nanomaterials is similar to that of mostbiological molecules and structures; therefore, nanomaterials can be useful for both in
vivo and in vitro biomedical research and applications. Thus far, the integration of
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iki/Nanomedicine#Neuro-electronic_interfaces%23Neuro-electronic_interfaceshttp://en.wikipedia.org/wiki/Nanomedicine#Medical_applications_of_molecular_nanotechnology%23Medical_applications_of_molecular_nanotechnologyhttp://en.wikipedia.org/wiki/Nanomedicine#Nanorobots%23Nanorobotshttp://en.wikipedia.org/wiki/Nanomedicine#Cell_repair_machines%23Cell_repair_machineshttp://en.wikipedia.org/wiki/Nanomedicine#Nanonephrology%23Nanonephrologyhttp://en.wikipedia.org/wiki/Nanomedicine#See_also%23See_alsohttp://en.wikipedia.org/wiki/Nanomedicine#References%23Referenceshttp://en.wikipedia.org/wiki/Nanomedicine#External_links%23External_linkshttp://en.wikipedia.org/w/index.php?title=Nanomedicine&action=edit§ion=1http://en.wikipedia.org/wiki/Nanobiotechnology 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nanomaterials with biology has led to the development of diagnostic devices, contrastagents, analytical tools, physical therapy applications, and drug delivery vehicles.
Nanomedicine seeks to deliver a valuable set of research tools and clinically usefuldevices in the near future.[3][4] TheNational Nanotechnology Initiative expects new
commercial applications in thepharmaceutical industrythat may include advanceddrug delivery systems, new therapies, and in vivo imaging.[5] Neuro-electronicinterfaces and othernanoelectronics-based sensors are another active goal of research.Further down the line, the speculativefield ofmolecular nanotechnology believes thatcell repair machines could revolutionize medicine and the medical field.
Nanomedicine is a large industry, with nanomedicine sales reaching $6.8 billion in2004, and with over 200 companies and 38 products worldwide, a minimum of $3.8
billion in nanotechnology R&D is being invested every year.[6] As the nanomedicineindustry continues to grow, it is expected to have a significant impact on theeconomy.
[edit] Medical use of nanomaterials
Two forms of nanomedicine that have already been tested in mice and are awaitinghuman trials that will be using gold nanoshells to help diagnose and treat cancer, andusing liposomes as vaccineadjuvants and as vehicles for drug transport.[7][8] Similarly,drug detoxification is also another application for nanomedicine which has shown
promising results in rats.[9] A benefit of using nanoscale for medical technologies isthat smaller devices are less invasive and can possibly be implanted inside the body,
plus biochemical reaction times are much shorter. These devices are faster and more
sensitive than typical drug delivery.[10]
[edit] Drug delivery
Nanotechnology has provided the possibility of delivering drugs to specific cellsusing nanoparticles. The overall drug consumption and side-effects may be loweredsignificantly by depositing the active agent in the morbid region only and in no higherdose than needed. This highly selective approach would reduce costs and humansuffering. An example can be found in dendrimers and nanoporous materials. Anotherexample is to use block co-polymers, which form micellesfor drug encapsulation.[11]They could hold small drug moleculestransporting them to the desired location.Another vision is based on small electromechanical systems;nanoelectromechanicalsystems are being investigated for the active release of drugs. Some potentiallyimportant applications include cancer treatment with iron nanoparticles or gold shells.A targeted or personalized medicine is intended to reduce the drug consumption andtreatment expenses resulting in an overall societal benefit by reducing the costs to the
public health system.
Nanomedical approaches to drug delivery center on developing nanoscale particles ormolecules to improve drugbioavailability. Bioavailability refers to the presence ofdrug molecules where they are needed in the body and where they will do the most
good. Drug delivery focuses on maximizing bioavailability both at specific places inthe body and over a period of time. This can potentially be achieved by molecular
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targeting by nanoengineered devices.[12][13] It is all about targeting the molecules anddelivering drugs with cell precision. More than $65 billion are wasted each year dueto poor bioavailability.In vivo imaging is another area where tools and devices are
being developed. Using nanoparticle contrast agents, images such as ultrasound andMRI have a favorable distribution and improved contrast. The new methods of
nanoengineered materials that are being developed might be effective in treatingillnesses and diseases such as cancer. What nanoscientists will be able to achieve inthe future is beyond current imagination. This might be accomplished by selfassembled biocompatible nanodevices that will detect, evaluate, treat and report to theclinical doctor automatically.
Drug delivery systems, lipid- or polymer-based nanoparticles,[14] can be designed toimprove thepharmacological and therapeutic properties of drugs.[15] The strength ofdrug delivery systems is their ability to alter thepharmacokinetics andbiodistributionof the drug. When designed to avoid the body's defence mechanisms, [16] nanoparticleshave beneficial properties that can be used to improve drug delivery. Where larger
particles would have been cleared from the body, cells take up these nanoparticlesbecause of their size. Complex drug delivery mechanisms are being developed,including the ability to get drugs through cell membranes and into cell cytoplasm.Efficiency is important because many diseases depend upon processes within the celland can only be impeded by drugs that make their way into the cell. Triggeredresponse is one way for drug molecules to be used more efficiently. Drugs are placedin the body and only activate on encountering a particular signal. For example, a drugwith poor solubility will be replaced by a drug delivery system where bothhydrophilic and hydrophobic environments exist, improving the solubility.[17] Also, adrug may cause tissue damage, but with drug delivery, regulated drug release caneliminate the problem. If a drug is cleared too quickly from the body, this could forcea patient to use high doses, but with drug delivery systems clearance can be reduced
by altering the pharmacokinetics of the drug. Poor biodistribution is a problem thatcan affect normal tissues through widespread distribution, but theparticulates fromdrug delivery systems lower the volume of distribution and reduce the effect on non-target tissue. Potential nanodrugs will work by very specific and well-understoodmechanisms; one of the major impacts of nanotechnology and nanoscience will be inleading development of completely new drugs with more useful behavior and less sideeffects.
It is greatly observed that[who?] nanoparticles are promising tools for the advancement
ofdrug delivery,medical imaging, and as diagnostic sensors. However, thebiodistribution of these nanoparticles is still imperfect due to the complex host'sreactions to nano- and microsized materials[14] and the difficulty in targeting specificorgans in the body. Nevertheless, a lot of work is still ongoing to optimize and betterunderstand the potential and limitations of nanoparticulate systems. For example,current research in the excretory systems of mice shows the ability of gold compositesto selectively target certain organs based on their size and charge. These compositesare encapsulated by a dendrimer and assigned a specific charge and size. Positively-charged gold nanoparticles were found to enter the kidneys while negatively-chargedgold nanoparticles remained in the liver and spleen. It is suggested that the positivesurface charge of the nanoparticle decreases the rate of opsonization of nanoparticles
in the liver, thus affecting the excretory pathway. Even at a relatively small size of5 nm, though, these particles can become compartmentalized in the peripheral tissues,
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and will therefore accumulate in the body over time. While advancement of researchproves that targeting and distribution can be augmented by nanoparticles, the dangersof nanotoxicity become an important next step in further understanding of theirmedical uses.[18]
[edit] Applications and reported research studies
Abraxane, approved by the U.S. Food and Drug Administration (FDA) to treat
breast cancerand non-small- cell lung cancer(NSCLC).[19] , is the nanoparticlealbumin bound paclitaxel.
In a mice study, scientists from Rice University and University of Texas MD
Anderson Cancer Centerreported enhanced effectiveness and reduced toxicityof an existing treatment forhead and neck cancerwhen using the nanoparticlesto deliver the drug. The hydrophiliccarbonic clusters functionalized with
polyethylene glycol or PEG-HCC are mixed with the chemotherapeutic drugpaclitaxel (Taxol) and the epidermal growth factor receptor(EGFR) targeted
Cetuximab and injected intravenously. They found the tumors were killedmore effectively with radiation and the healthy tissue suffered less toxicitythan without the nanotechnology drug delivery. The standard treatmentcontains Cremophor EL which allows the hydrophobicpaclitaxel to bedelivered intravenously. Replacing the toxic Cremophor with carbonnanoparticles eliminated its side effect and improved drug targeting which inturn required a lower dose of the toxic paclitaxel.[20]
Researchers atCase Western Reserve Universityreported using nanoparticle
chain to deliverdoxorubicin to breast cancer cells in a mice study. Threemagnetic, iron-oxide nanospheres were chemically linked to one doxorubicin-
loaded liposome and formed a 100 nm long nanoparticle chain. After thenanochains penetrated the tumor, radiofrequency field was generated thatcaused the magnetic nanoparticles to vibrate and rupture the liposome,dispersing the drug in its free form throughout the tumor. The result showedthat the nano treatment was more effective in halting tumor growth than thestandard treatment with doxorubicin. It is also less harmful to healthy cellssince only 5% to 10% of the standard dose of doxorubicin were used.[21][22]
Nanoparticles made ofpolyethylene glycol (PEG) carrying payload of
antibiotics at its core could swift chargethus allowing them to target bacterialinfection more precisely inside the body, a group ofMITresearchers reported.The nanoparticles, containing a sub-layer ofpH sensitive chains of the amino
acidhistidine, carry a slightly negative charge when circulating in the bloodstream, can evade detection and clearing by the immune system. When theyencounter an infection site the particles gain a positive charge provoked by theslightly acidic environment at the infection sites, allowing them to bind to thenegatively charged bacterial cell walls and release antibiotics at locally highconcentration. This nano delivery system can potentially destroy bacteria evenit has developed resistance to antibiotics because of the targeted high dose and
prolonged release of the drug. Although a lot of work is still needed, theresearchers believe that it points to a new direction of using nanotechnology totreat infectious disease.[23][24]
Using thebiomimetic strategy, researchers in the Harvard UniversityWyss
Institute demonstrated in a mouse model that the drug coated nanoparticlescan dissolve blood clots by selectively binding to the narrowed regions in the
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blood vessels just like theplateletsdo.[25] Aggregates of biodegradablenanoparticles coated withtissue plasminogen activator(tPA), each about thesize of a platelet, were injectedintravenously. In the region of vesselnarrowing, shear stresses dissociate the aggregates and release the tPA-coatednanoparticles which bind and degrade the blood clots. By prcised targeting
and concentrating drug at the location of obstruction, the dose used is less than1/50th of the normal dose. The nanotherapeutics will greatly reduce the severeside effect of bleeding, commonly found in standard treatment ofthrombosis.[25]
The X-shaped RNA nanoparticles capable of carrying four functional modules
were created by researchers in the University of Kentucky. These RNAmolecules are chemically and thermodynamically stable, able to remain intactin the mouse body for more than 8 hours and to resist degradation by RNase inthe blood stream. With its four arms attached with a combination of differentactive agents, for example, iRNA (forgene silencing),microRNA (forgeneexpression regulation), aptamer(for targeting) andribozyme (as catalyst), the
X-shaped RNA can achieve therapeutic and diagnostic functions by regulatinggene expression and cellular function, and binding to cancer cells with
precision, enhanced by its polyvalent nature and synergistic effects by design.[26][27]
An early phase clinical trial using the platform of Minicell nanoparticle for
drug delivery have been tested on patients with advanced and untreatablecancer. Built from the membranes of mutant bacteria, the minicells wereloaded withpaclitaxel and coated with cetuximab, antibodies that bind theepidermal growth factor receptor(EGFR) which is often overexpressed in anumber of cancers, as a homing device to the tumor cells. The tumor cellsrecognize the bacteria from which the minicells have been derived, regard it asinvading microorganism and engulf it. Once inside, the payload of anti-cancerdrug kills the tumor cells. Measured at 400 nanometers, the minicell is biggerthan synthetic particles developed for drug delivery. The researchers indicatedthat this larger size give the minicells a better profile in side-effects becausethe minicells will preferentially leak out of the porous blood vessels aroundthe tumor cells and do not reach the liver, digestive system and skin. ThisPhase 1 clinical trial demonstrated that this treatment is well tolerated by the
patients. As a platform technology, the minicell drug delivery system can beused to treat a number of different cancers with different anti-cancer drugswith the benefit of lower dose and less side-effects.[28][29]
[edit] Protein and peptide delivery
Protein and peptides exert multiple biological actions in human body and they havebeen identified as showing great promise for treatment of various diseases anddisorders. These macromolecules are calledbiopharmaceuticals. Targeted and/orcontrolled delivery of these biopharmaceuticals using nanomaterialslike nanoparticlesand Dendrimers is an emerging field called nanobiopharmaceutics, and these productsare called nanobiopharmaceuticals.
[edit] Applications and reported research studies
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Nanoparticles delivering the myelin antigens were found to induce immune
tolerance in a mouse model with relapsing multiple sclerosis.Biodegradablepolystyrene microparticles coated with the myelin sheathpeptides reset themouses immune system and prevent the disease from recurring or reduce thesymptoms by halting the attack of the immune system to the protective myelin
sheath coating the nerve fibers of the central nervous system. Team ofresearchers inNorthwestern Universityindicated that this treatment methodcan potentially be used in otherautoimmune diseases.[30][31]
[edit] Cancer
A schematic illustration showing how nanoparticles or other cancer drugs might beused to treat cancer.
The small size of nanoparticles endows them with properties that can be very useful inoncology, particularly in imaging. Quantum dots (nanoparticles with quantumconfinement properties, such as size-tunable light emission), when used inconjunction with MRI (magnetic resonance imaging), can produce exceptional imagesof tumor sites. These nanoparticles are much brighter than organic dyes and only needone light source for excitation. This means that the use of fluorescent quantum dotscould produce a higher contrast image and at a lower cost than today's organic dyes
used as contrast media. The downside, however, is that quantum dots are usuallymade of quite toxic elements.
Another nanoproperty, high surface area to volume ratio, allows many functionalgroups to be attached to a nanoparticle, which can seek out and bind to certaintumorcells. Additionally, the small size of nanoparticles (10 to 100 nanometers), allowsthem to preferentially accumulate at tumor sites (because tumors lack an effectivelymphatic drainage system). A very exciting research question is how to make theseimaging nanoparticles do more things for cancer. For instance, is it possible tomanufacture multifunctional nanoparticles that would detect, image, and then proceed
to treat a tumor? This question is under vigorous investigation; the answer to whichcould shape the future of cancer treatment. [32] A promising new cancer treatment that
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may one day replace radiation and chemotherapy is edging closer to human trials.Kanzius RF therapy attaches microscopic nanoparticles to cancer cells and then"cooks" tumors inside the body with radio waves that heat only the nanoparticles andthe adjacent (cancerous) cells.
Sensor test chips containing thousands of nanowires, able to detect proteins and otherbiomarkers left behind by cancer cells, could enable the detection and diagnosis ofcancer in the early stages from a few drops of a patient's blood.[33]
The basic point to use drug delivery is based upon three facts: a) efficientencapsulation of the drugs, b) successful delivery of said drugs to the targeted regionof the body, and c) successful release of that drug there.
Researchers atRice Universityunder Prof. Jennifer West, have demonstrated the useof 120 nm diameternanoshells coated with gold to kill cancer tumors in mice. Thenanoshells can be targeted to bond to cancerous cells by conjugating antibodies or
peptides to the nanoshell surface. By irradiating the area of the tumor with an infraredlaser, which passes through flesh without heating it, the gold is heated sufficiently tocause death to the cancer cells.[34]
Nanoparticles ofcadmium selenide (quantum dots) glow when exposed to ultravioletlight. When injected, they seep into cancertumors. The surgeon can see the glowingtumor, and use it as a guide for more accurate tumor removal.
Inphotodynamic therapy, a particle is placed within the body and is illuminated withlight from the outside. The light gets absorbed by the particle and if the particle ismetal, energy from the light will heat the particle and surrounding tissue. Light mayalso be used to produce high energy oxygen molecules which will chemically reactwith and destroy most organic molecules that are next to them (like tumors). Thistherapy is appealing for many reasons. It does not leave a toxic trail of reactivemolecules throughout the body (chemotherapy) because it is directed where only thelight is shined and the particles exist. Photodynamic therapy has potential for anoninvasive procedure for dealing with diseases, growth and tumors.
[edit] Surgery
At Rice University, a flesh welder is used to fuse two pieces of chicken meat into a
single piece. The two pieces of chicken are placed together touching. A greenishliquid containing gold-coated nanoshells is dribbled along the seam. An infrared laseris traced along the seam, causing the two sides to weld together. This could solve thedifficulties and blood leaks caused when the surgeon tries to restitch the arteries thathave been cut during a kidney or heart transplant. The flesh welder could weld theartery perfectly.[35]
[edit] Visualization
Tracking movement can help determine how well drugs are being distributed or howsubstances are metabolized. It is difficult to track a small group of cells throughout
the body, so scientists used to dye the cells. These dyes needed to be excited by lightof a certain wavelength in order for them to light up. While different color dyes
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absorb different frequencies of light, there was a need for as many light sources ascells. A way around this problem is with luminescent tags. These tags arequantumdots attached to proteins that penetrate cell membranes. The dots can be random insize, can be made of bio-inert material, and they demonstrate the nanoscale propertythat color is size-dependent. As a result, sizes are selected so that the frequency of
light used to make a group of quantum dots fluoresce is an even multiple of thefrequency required to make another group incandesce. Then both groups can be litwith a single light source.
[edit] Tissue engineering
Nanotechnology may be able to help reproduce or repair damaged tissue. Tissueengineering makes use of artificially stimulated cell proliferation by using suitablenanomaterial-based scaffolds and growth factors. For example, bones could beregrown on carbon nanotube scaffolds.[36] Tissue engineering might replace today'sconventional treatments like organ transplants or artificial implants. Advanced formsof tissue engineering may lead to life extension.[citation needed]
[edit] Antibiotic resistance
Nanoparicles can be used in combination therapy for decreasing antibiotic resistance.It has been shown that Zinc Oxidenanoparticles can decrease the antibiotic resistanceand enhance the antibacterial activity ofCiprofloxacinagainst microorganisminVitro. Nanoparticles can interfere with the different proteins which are interacting inthe antibiotic resistance or pharmacologic mechanisms of drugs.[37]
[edit] Immune response
Buckyballs have been investigated for the ability to "interrupt" the allergy/immuneresponse by preventing mast cells (which cause allergic response) from releasinghistamine into the blood and tissues, by binding to free radicals "dramatically betterthan any anti-oxidant currently available, such as vitamin E".[38]
[edit] Diagnostic and medical devices
Nanotechnology-on-a-chip is one more dimension oflab-on-a-chip technology.
Magnetic nanoparticles, bound to a suitable antibody, are used to label specificmolecules, structures or microorganisms. Gold nanoparticles tagged with shortsegments ofDNA can be used for detection of genetic sequence in a sample.Multicolor optical coding for biological assays has been achieved by embeddingdifferent-sized quantum dots into polymeric microbeads. Nanopore technology foranalysis of nucleic acids converts strings of nucleotides directly into electronicsignatures.[citation needed]
Nanotechnology is also opening up new opportunities in implantable deliverysystems, which are often preferable to the use of injectable drugs, because the latterfrequently display first-order kinetics (the blood concentration goes up rapidly, but
drops exponentially over time). This rapid rise may cause difficulties with toxicity,
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and drug efficacy can diminish as the drug concentration falls below the targetedrange.[citation needed]
[edit] Neuro-electronic interfaces
Neuro-electronic interfacing is a visionary goal dealing with the construction ofnanodevices that will permit computers to be joined and linked to the nervous system.This idea requires the building of a molecular structure that will permit control anddetection of nerve impulses by an external computer. The computers will be able tointerpret, register, and respond to signals the body gives off when it feels sensations.The demand for such structures is huge because many diseases involve the decay ofthe nervous system (ALS and multiple sclerosis). Also, many injuries and accidentsmay impair the nervous system resulting in dysfunctional systems and paraplegia. Ifcomputers could control the nervous system through neuro-electronic interface,
problems that impair the system could be controlled so that effects of diseases and
injuries could be overcome. Two considerations must be made when selecting thepower source for such applications. They are refuelable and nonrefuelable strategies.A refuelable strategy implies energy is refilled continuously or periodically withexternal sonic, chemical, tethered, magnetic, or electrical sources. A nonrefuelablestrategy implies that all power is drawn from internal energy storage which wouldstop when all energy is drained.
One limitation to this innovation is the fact that electrical interference is a possibility.Electric fields, electromagnetic pulses (EMP), and stray fields from otherin vivoelectrical devices can all cause interference. Also, thick insulators are required to
prevent electron leakage, and if high conductivity of the in vivo medium occurs there
is a risk of sudden power loss and shorting out. Finally, thick wires are also neededto conduct substantial power levels without overheating. Little practical progress has
been made even though research is happening. The wiring of the structure isextremely difficult because they must be positioned precisely in the nervous system sothat it is able to monitor and respond to nervous signals. The structures that will
provide the interface must also be compatible with the bodys immune system so thatthey will remain unaffected in the body for a long time.[39] In addition, the structuresmust also sense ionic currents and be able to cause currents to flow backward. Whilethe potential for these structures is amazing, there is no timetable for when they will
be available.
[edit] Medical applications of molecular
nanotechnology
Molecular nanotechnology is a speculativesubfield of nanotechnology regarding thepossibility of engineering molecular assemblers, machines which could re-ordermatter at a molecular or atomic scale. Molecular nanotechnology is highly theoretical,seeking to anticipate what inventions nanotechnology might yield and to propose anagenda for future inquiry. The proposed elements of molecular nanotechnology, suchas molecular assemblers and nanorobotsare far beyond current capabilities.
[edit] Nanorobots
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The somewhat speculative claims about the possibility of using nanorobots[40] inmedicine, advocates say, would totally change the world ofmedicine once it isrealized. Nanomedicine[1][39] would make use of these nanorobots (e.g., ComputationalGenes), introduced into the body, to repair or detect damages and infections.According to Robert Freitasof the Institute for Molecular Manufacturing, a typical
blood borne medical nanorobot would be between 0.5-3 micrometres in size, becausethat is the maximum size possible due to capillary passage requirement. Carbon could
be the primary element used to build these nanorobots due to the inherent strength andother characteristics of some forms of carbon (diamond/fullerenecomposites), andnanorobots would be fabricated in desktop nanofactories [41] specialized for this
purpose.
Nanodevices could be observed at work inside the body using MRI, especially if theircomponents were manufactured using mostly 13C atoms rather than the natural 12Cisotope of carbon, since 13C has a nonzero nuclear magnetic moment. Medicalnanodevices would first be injected into a human body, and would then go to work in
a specific organ or tissue mass. The doctor will monitor the progress, and makecertain that the nanodevices have gotten to the correct target treatment region. Thedoctor will also be able to scan a section of the body, and actually see the nanodevicescongregated neatly around their target (a tumor mass, etc.) so that he or she can besure that the procedure was successful.
[edit] Cell repair machines
This article may containoriginal research. Please improve it by verifying theclaims made and addingreferences. Statements consisting only of original
research may be removed. (January 2009)
Using drugs and surgery, doctors can only encourage tissues to repair themselves.With molecular machines, there will be more direct repairs.[42] Cell repair will utilizethe same tasks that living systems already prove possible. Access to cells is possible
because biologists can insert needles into cells without killing them. Thus, molecularmachines are capable of entering the cell. Also, all specific biochemical interactionsshow that molecular systems can recognize other molecules by touch, build or rebuildevery molecule in a cell, and can disassemble damaged molecules. Finally, cells thatreplicate prove that molecular systems can assemble every system found in a cell.Therefore, since nature has demonstrated the basic operations needed to perform
molecular-level cell repair, in the future, nanomachine based systems will be built thatare able to enter cells, sense differences from healthy ones and make modifications tothe structure.
The healthcare possibilities of these cell repair machines are impressive. Comparableto the size of viruses or bacteria, their compact parts would allow them to be morecomplex. The early machines will be specialized. As they open and close cellmembranes or travel through tissue and enter cells and viruses, machines will only beable to correct a single molecular disorder like DNA damage or enzyme deficiency.Later, cell repair machines will be programmed with more abilities with the help ofadvanced AI systems.
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Nanocomputers will be needed to guide these machines. These computers will directmachines to examine, take apart, and rebuild damaged molecular structures. Repairmachines will be able to repair whole cells by working structure by structure. Then byworking cell by cell and tissue by tissue, whole organs can be repaired. Finally, byworking organ by organ, health is restored to the body. Cells damaged to the point of
inactivity can be repaired because of the ability of molecular machines to build cellsfrom scratch. Therefore, cell repair machines will free medicine from reliance on selfrepair alone.
[edit] Nanonephrology
Nanonephrology is a branch of nanomedicine and nanotechnology that seeks to usenano-materials and nano-devices for the diagnosis, therapy, and management of renaldiseases. It includes the following goals:
1. the study of kidney protein structures at the atomic level2. nano-imaging approaches to study cellular processes in kidney cells3. nano medical treatments that utilize nanoparticles to treat various kidney
diseases
Advances in Nanonephrology are expected to be based on discoveries in the aboveareas that can provide nano-scale information on the cellular molecular machineryinvolved in normal kidney processes and in pathological states. By understanding the
physical and chemical properties of proteins and other macromolecules at the atomiclevel in various cells in the kidney, novel therapeutic approaches can be designed tocombat major renal diseases. The nano-scale artificial kidney is a goal that many
physicians dream of. Nano-scale engineering advances will permit programmable andcontrollable nano-scale robots to execute curative and reconstructive procedures in thehuman kidney at the cellular and molecular levels. Designing nanostructurescompatible with the kidney cells and that can safely operate in vivo is also a futuregoal. The ability to direct events in a controlled fashion at the cellular nano-level hasthe potential of significantly improving the lives of patients with kidney diseases.
when giving a drug to a patient, it circulates in the blood stream, but often doesn't get into thetissue," said senior author Erkki Ruoslahti, of the Burnham Institute for Medical Research atUCSB. "This is especially true with tumors."We believe this method will lead to better, more efficient delivery of drugs," he said. In thisstudy, the scientists used prostate cancer cells as their target, but the method could apply toany type of cell.The scientists developed a peptide, a small piece of protein that can carry "cargo" for deliveryinto the cell. The cargo could be a nanoparticle, or even a cell. Riding on the peptide, thecargo gets out of the blood vessel and penetrates the tissue.The drug is located at one end of the peptide. At the other is the "C terminal," which has the"motif" an amino acid sequence including arginine or lysine, that causes the tissue
penetration. This terminal has to be open, the researchers found. The strict requirement for
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the C terminal led the group to coin a new name, the "C-end rule," or CendR, pronounced"sender
Polymeric nanoparticles have demonstrated enormous potential as cellular drug
delivery vehicles. Nanoparticles improve drug's stability as well as its availability andretention at the target intracellular site of action. Therapeutic efficacy of nanoparticlescan be further enhanced by conjugating specific ligands to nanoparticle surface.Ligand conjugation can also be used to favorably modify the intracellular dispositionof nanoparticles. A number of ligands are available for this purpose; use of a specificligand depends on the target cell, the material used for nanoparticle formulation, andthe chemistry available for ligand-nanoparticle conjugation. Cellular drug deliveryusing nanoparticles is also affected by clearance through the reticuloendothelialsystem. In this paper, we review the recent progress on our understanding of
physicochemical factors that affect the cellular uptake of nanoparticles and thedifferent cellular processes that could be exploited to enhance nanoparticle uptake
into
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Multi-Functional Nanoparticles and Their Role in
Cancer Drug Delivery A Review
Priya Pathak and V. K. KatiyarCopyright AZoM.com Pty Ltd.
This is an AZo Open Access Rewards System (AZo-OARS) article distributed under
the terms of the AZoOARS http://www.azonano.com/oars.asp which permits
unrestricted use provided the original work is properly cited but is limited to non-
commercial distribution and reproduction.
Submitted: April 10, 2007
Posted: May 11, 2007
Topics CoveredAbstract
Introduction
The Evolution of Nanotechnology
The Vision for Nanoparticles in the Treatment of CancerWorld Scenario: Case of Cancer
The Incidence of Cancer in Our Society
Factors Effecting the Incidence of Cancer
Projected Growth of Cancer in the Future
Structure and Functional Properties of Nanoparticles
Size, Toxicity, Status and Application of Nanoparticles in Cancer Treatment
Types of Biomedical Nanoparticles
Multifunctional Nanoparticles
Lipid/Polymer Nanoparticles
Gold / Magnetic Nanoparticles
Virus Based Nanoparticles
Dry Powder Aerosol
Nanomedicine
Drug Delivery for Cancer Treatment
Drug Delivery Strategies Used to Fight Cancers
Pathways of Nanoparticles in Cancer Drug Delivery
Characteristic Nanoparticles Used for Drug Delievry in Cancer Treatment
The Role of Nanoparticles in Cancer Drug Delivery
Nanodevices: Detection and Cure
Cantilevers
Nanopores
Nanotubes
Quantum Dots (QDs)
Nanoshells
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Dendrimers
Biodegradable Hydrogels
Future Herbal Nanoparticles for Cancer
Development and Commercialization of Nanomaterials
Companies Involved with the Commercialization of Nanomaterials for Bio-
and Medical ApplicationsConclusion
Acknowledgement
References
Contact Details
AbstractNanomaterials are at the cutting edge of the rapidly developing area of
nanotechnology. The potential for nanoparticles in cancer drug delivery is infinite
with novel new applications constantly being explored. Multifunctional
nanoparticles play a very significant role in cancer drug delivery. The promising
implications of these platforms for advances in cancer diagnostics and
therapeutics form the basis of this review.
In the first part, we examine cancer on the world stage, nanoparticles and their
structure, functional properties, biomedical applications, nanomedicine, cancer
drug delivery and drug delivery strategies using nanoparticles. In the second
part, we focus on the various pathways available for cancer drug delivery and the
role of nanoparticles in cancer drug delivery. In last part, the use of nanodevices
in detection and imaging of cancer are discussed along with the
commercialization of nanomaterials. The review provides recent advances in
cancer drug delivery.
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Introduction
Cancer has a physiological barrier [1,2] like vascular endothelial pores,
heterogeneous blood supply, heterogeneous architecture etc. For a treatment to
be successful, it is very important to get over these barriers. Cancer represents
an enormous biomedical challenge [3] for drug delivery. Cancer treatment is very
much dependent on the method of delivery. In the past, cancer patients were
using various anticancer drugs, but these drugs were less successful and had
major side effects. Nanoparticles have attracted the attention of scientists
because of their multifunctional character. The treatment of cancer using targeted
drug delivery nanoparticles is the latest achievement in the medical field.
The Evolution of Nanotechnology
The Nanoscale was initially used by R. P. Feynman, a physicist. In his talk, 1959,
called Theres plenty of room at the bottom. But theres not that much room - to
put every atom in its place - the vision articulated by some nanotechnologists -
would require magic fingers. He was one of the first people to suggest that
scaling down to nano level and starting from the bottom was the key to future
technology and advancement [4, 5].
The Vision for Nanoparticles in theTreatment of Cancer
In ancient Greek Nano means dwarf [6]. Nanotechnology is the creation and
utilization of materials, devices, and systems through the control of matter on the
nanometer-length scale, i.e. at the level of atoms, molecules, and supramolecular
structures. These technologies have been applied to improve drug delivery and to
overcome some of the problems of drug delivery for cancer treatment. Several
nanobiotechnologies mostly based on nanoparticles, have been used to facilitate
drug delivery in cancer. The magic of nanoparticles mesmerize everyone because
of their multifunctional character and they have given us hope for the recovery
from this disease. Although we are practicing better drug delivery paths into the
body, we ultimately seek more accurate protocols to eradicate cancer from our
society.
This review focuses on progress in treatment of cancer through delivery of
anticancer agents via nanoparticles. In addition, it pays attention to development
of different types of nanoparticles for cancer drug delivery.
World Scenario: Case of Cancer
The Incidence of Cancer in Our Society
With more than 10 million new cases every year, cancer has become one of the
most devastating diseases worldwide [7]. In 2000, it has been reported by TheWorld Health Organization (WHO), malignant tumors were responsible for 12 per
cent of the nearly 56 million deaths worldwide from all causes. Over 22 million
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Contact Details
Cancer nanotherapeutics are rapidly progressing and are being implemented to solve severallimitations of conventional drug delivery systems such as nonspecificbiodistribution and targeting,lack of water solubility, poor oral bioavailability, and low therapeutic indices. To improve thebiodistributionof cancer drugs, nanoparticles have been designed for optimal size and surfacecharacteristics to increase their circulation time in the bloodstream. They are also able to carry their
loaded active drugs to cancer cells by selectively using the unique path physiology of tumors, such astheir enhanced permeability and retention effect and the tumor microenvironment. In addition to thispassive targeting mechanism, active targeting strategies using ligands or antibodies directed againstselected tumor targets amplify the specificity of these therapeutic nanoparticles.Drug resistance,another obstacle that impedes the efficacy of bothmolecularly targeted and conventionalchemotherapeutic agents, might also be overcome, or at least reduced, usingnanoparticles.Nanoparticles have the ability to accumulate in cells without being recognized byP-glycoprotein, one of themainmediatorsofmultidrug resistance, resulting in the increase intracellularconcentration of drugs. Multifunctional and multiplex nanoparticles are nowbeing activelyinvestigated and are on the horizon as the next generation of nanoparticles, facilitating personalizedand tailored cancer treatment
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