Can developing countries use nanotechnology to improve health? Priya Shetty looks at nanomedicine's promise.
Nanotechnology — the science of the extremely small — holds enormous potential for healthcare, from delivering drugs more effectively, diagnosing diseases more rapidly and sensitively, and delivering vaccines via aerosols and patches.
Nanotechnology is the science of materials at the molecular or subatomic level. It involves manipulation of particles smaller than 100 nanometres (one nanometre is one-billionth of a metre) and the technology involves developing materials or devices within that size — invisible to the human eye and often many hundred times thinner than the width of human hair. The physics and chemistry of materials are radically different when reduced to the nanoscale; they have different strengths, conductivity and reactivity, and exploiting this could revolutionise medicine.
For example, a major challenge of modern medicine is that the body doesn't absorb the entire drug dose given to a patient. Using nanotechnology, scientists can ensure drugs are delivered to specific areas in the body with greater precision, and the drugs can be formulated so that the active ingredient better permeates cell membranes, reducing the required dose (see panel 1).
Rich countries are investing heavily in nanotechnology for health. The first generation of cancer drugs delivered via nanoparticles, for example, has already been approved by the US Food and Drug Administration (FDA).
However, it is still early days for nanotechnology in healthcare and whether it will be of value to resource-poor countries is still hotly debated. Critics argue that when millions of people in countries like India or those in Sub-Saharan Africa are dying because of a lack of access to even basic healthcare, investing in cutting-edge technologies is a ludicrous waste of money. 
And experts are concerned that the toxicity of nanoparticles to human health and the environment has not been studied extensively enough. For instance, a 2004 report by the UK Royal Society and Royal Academy of Engineering recommended that nanoparticles and nanotubes — cylindrical carbon molecules that are better conductors than normal carbon molecules — be treated as hazardous waste. 
Many emerging economies such as Brazil, China, India, Iran, Malaysia, Mexico, Singapore and South Africa have ambitious research and development (R&D) plans for nanotechnology. Their governments need to balance short-term health needs with long-term technological investment.
Yet while poor countries have an ongoing responsibility to strengthen healthcare systems and provide wider access to medicine, nanotechnology could, in the long run, save lives by making diagnosis and treatment far more effective.
A group of scientists who have mapped out the uses of nanotechnology and the needs of global health argue that nanomedicine is relevant for the developing world. They surveyed researchers worldwide and concluded that nanotechnology could greatly contribute to meeting the Millennium Development Goals for health. Specifically, the goals to reduce child mortality, improve maternal mortality and combat HIV/AIDS, malaria and other diseases. 
Diagnostics and screening
There is an urgent need in the developing world for better disease diagnosis, and nanotechnology offers a multitude of options for detecting disease (see panel 1 on uses for nanotechnology).
Fluorescent quantum dots could improve malaria diagnosis by targeting the blood cell's inner membrane.
One way of doing this is by using quantum dots — nanosized semiconductors that can be used as biosensors to find disease and which can be made to fluoresce. Sometimes known as nanocrystals, quantum dots have significant advantages over traditional organic dyes as their luminescence can be tuned to a wide range of frequencies, and they degrade much more slowly in the body. Fluorescent quantum dots can be tagged to antibodies that target cancerous cells or cells infected with tuberculosis (TB) or HIV (see panel 3 on nanotechnology and tuberculosis). [4, 5]
Fluorescent quantum dots could also be used to diagnose malaria by making them target the protein that forms a mesh in the blood cell's inner membrane. The shape of this protein network changes when cells are infected with malaria, so scientists are able to spot malaria infection from the shape produced by the dots. 
Similarly, carbon nanotubes, and other nanoparticles such as nanowires, have been used as biosensors to detect diseases such as HIV and cancer. Cancer biosensors can be made, for instance, by attaching nucleic acid probes to the ends of nanowires. These probes are specifically designed to bond to biomarkers that indicate cancer such as mutated RNA. When mutated RNA in a sample interacts with the probes, electric currents are induced along the nanowire, which is detected by the silicon chip in which the biosensor is embedded. 
Nanotechnology could also revolutionise drug delivery by overcoming challenges such as how to sustain the release of drugs in the body and improving bioavailability — the amount of active ingredient per dose.
Some drugs can now be delivered through 'nanovehicles'. For example liposomes, which can deliver the drug payload by fusing with cell membranes, have been used to enscapsulate HIV drugs such as stavudine and zidovudine in vehicles ranging from 120 to 200 nanometres in size.  Since both these drugs have short half-lives, the liposome coating could potentially make them active for longer periods.
Other nanodrug delivery systems include using fullerene 'buckyball' cages,  and branched nanomolecules called dendrimers (see panel).
Panel 1. Uses for nanotechnology in health
There are several developments in nanotechnology that can help improve health in developing countries.
Disease diagnosis and screening
- Nanolitre systems (known as lab-on-a-chip): devices that automate a biological process using fluids at the nanolitre scale.
- Quantum dots: nanosized semiconductors that can be used as biosensors to find disease. Because they fluoresce they can be used to tag diseased cells.
- Magnetic nanoparticles: used as nanosensors
- Nanosensor arrays: grids of carbon nanotubes
- Antibody-dendrimer conjugates: branched nanomolecules with antibodies on their ends for diagnosis of HIV and cancer
- Carbon nanotubes and flatter, thin wires called nanobelts or nanowires (often made of gold) as nanosensors for disease diagnosis as they bond to biomarkers that indicate cancer such as mutated RNA
- Nanoparticles as medical image enhancers: medical imaging relies on looking for contrasts in the way light is scattered in healthy tissue compared with diseased tissue. The sharper this contrast, the more accurate the diagnosis. Nanoparticles are able to give medical imaging techniques a sharper resolution, making it easier to identify disease.
Drug delivery systems
The choice of system depends on the way they bind with the drug and the type of drug treatment.
- Nanocapsules: these are pods that encapsulate drugs, which ensures the drugs are released more slowly and steadily in the body
- Liposomes: artificial vesicles made up of a lipid bilayer so they can fuse with and penetrate membranes easily. These have been used to treat diseases such cancer, fungal infections, hepatitis A, and influenza.
- Dendrimers: tree-shaped synthetic nanomolecules that carry drugs in the tips of the branches.
- Buckyballs: spherical nanoparticles can carry more than one drug at a time. They are useful in the treatment of diseases such as cancer and other diseases where monotherapy can lead to drug resistance
- Nanobiomagnets which carry drugs, for cancer for instance, into the body and are held at the target site by an external magnet. The purpose of this is to concentrate the drug at the tumour site for long enough for it to be absorbed.
- Attapulgite clays with nanometre-sized pores that are ideal for filtering out harmful bacteria from water
- Nanotechnology can also provide alternatives to injectable vaccines if the inactive virus is bound up with nanoparticles to increase the immune response.
Nanotubes and nanoparticles can be used as glucose, carbon dioxide and cholesterol sensors and for in-situ monitoring of homeostasis, the process by which the body maintains metabolic equilibrium.
In the developed world, cancer is top of the list of diseases being targeted for nanomedical treatment (see panel 2 on cancer). Cancer prevalence is rising fast in the developing world with 70 per cent of all cancer deaths, according to WHO. In developing nations, the use of nanotechnology is also being explored in the fight against infectious diseases such as HIV and TB.
Panel 2: Could nanotech help cure cancer?
Nanotechnology advances have been heavily focused on cancer, mainly on diagnosis and drug delivery.
Drugs carried by polymer-coated nanoparticles have been used to treat multidrug-resistant breast and ovarian cancer with the chemotherapies paclitaxel, which inhibits cell division, and lonidamine, which suppresses energy metabolism in cancer cells. The nanoparticles are designed to target an epidermal growth factor receptor, which is overexpressed in tumour cells. 
Detecting cancer early can make a significant difference to the survival rate. Using magnetic nanoparticles in a miniature magnetic resonance sensor is so sensitive, scientists can detect as few as two cancer cells in one microlitre of a biosample, radically increasing early detection. 
Scientists at Stanford University in the United States have used nanotechnology to devise a highly specific method of killing cancerous cells. They inserted carbon nanotubes into cancer cells and then exposed the tissue to near-infrared laser light, heating up the nanotubes and killing the cancer cells while leaving the healthy cells intact. 
Panel 3: Tuberculosis and nanotechnology
The Central Scientific Instruments Organisation of India has designed a nanotechnology-based TB diagnostic kit, currently undergoing clinical trials. This would cut both the cost and time required for TB tests, and also require a smaller amount of blood for testing.
Nanotechnology is also being used to treat TB more effectively. Existing TB treatment requires a complex drug regimen delivered over a period of months. Many patients don't take the drugs properly or fail to complete the course. Drug formulations based on nanotechnology degrade more slowly, allowing more of the active ingredient to be delivered so that fewer doses are required.
The drugs are encapsulated in biodegradable polymers such as liposomes and microspheres, which ensure sustained delivery of the medicine. Nanoparticles of polylactide co-glycolide, a polymer often used to deliver drugs since it degrades well and doesn't cause an immune reaction, have been successfully tested as drug carriers for TB by groups at US-based Harvard University, the Postgraduate Institute of Medical Education and Research in India and the Council for Scientific and Industrial Research in South Africa.
Nanoparticles could also be the basis for delivering an aerosol TB vaccine. Needle-free, and therefore not requiring trained personnel to administer it, the vaccine is stable at room temperatures — important in rural areas that lack a reliable cold chain.
Nanotechnology could herald a new era in immunisation by providing alternatives to injectable vaccines for diseases that affect the poor. Injectable vaccines need to be administered by healthcare professionals, who may be scarce in developing countries, particularly in rural areas. Vaccines also need reliable refrigeration along the delivery chain. Scientists are working on an aerosol TB vaccine (see panel 3). They are also investigating a nanotechnology-based skin patch against West Nile Virus and Chikungunya virus. 
Nanotechnology can provide alternatives to injectable vaccines that rely on healthcare professionals to administer
Injectable vaccines can be useful if the inactive virus is bound up with nanoparticles to increase the immune response. This method is being used to devise a vaccine against pandemic influenza. 
Leaders of the pack
China is by far top of the leader board for nanotechnology research among developing countries, registering the most nanotechnology patents. It has had a national nanotechnology programme since the early 1990s, and a huge number of new nanotechnology companies are set up every year. 
India is also taking nanotechnology seriously, with over 30 institutions involved in research. South-East Asian countries are especially active, with Malaysia, the Philippines, Thailand and Vietnam all engaged in nanotechnology research.
In Africa, meanwhile, South Africa has both its private and public sector working on nanotechnology R&D. Brazil, which is leading nanotechnology research in Latin America, has partnered with South Africa and India to promote South–South collaboration through the IBSA Nanotechnology Initiative.
Many other developing nations are hoping to catch up. A 2005 survey of global nanotechnology research activity classed countries as having national activities or funding (suggesting a clear national strategy or government funding), having at least one individual or research group engaged in nanotechnology research, or having the government expressing an interest in pursuing nanotechnology (see table 1, adapted from ).
Nanotechnology is an expensive science but the costs of setting up an institute seem to vary widely between countries. For instance, Mexico and Vietnam say it costs about US$5 million to establish a nanotechnology institute, but Costa Rica says it has done so for less than US$500,000. 
National activity or funding
Argentina; Armenia; Brazil; Chile; China; Cost Rica; Egypt; Georgia; India; Iran; Mexico; Malaysia; Philippines; Serbia & Montenegro; South Africa, Thailand, Turkey; Uruguay; Vietnam
Belarus; Bulgaria; Cyprus; Czech Republic; Estonia; Hong Kong; Hungary; Israel; Latvia; Lithuania; Poland, Romania; Russian Federation; Singapore; Slovak Republic; Slovenia; South Korea; Ukraine
Individual or group research
Botswana; Columbia; Croatia; Cuba; Indonesia; Jordan; Kazakhstan; Moldova; Pakistan; Uzbekistan; Venezuela
Macau, (China); Malta; United Arab Emirates
Afghanistan; Senegal; Tanzania
Albania; Bosnia and Herzegovina; Ecuador; Ghana; Kenya; Lebanon; Macedonia; Sri Lanka; Swaziland; Zimbabwe
Table 1: Nanotechnology league table
What is technically possible and what is ethically appropriate is a matter of heated debate. In developing nations, nanomedicine evokes similar ethical issues to genetically modified foods. When people are desperately in need of food or medicine does it matter through what route it arrives? And whether illiterate or uneducated populations can be adequately involved in debates about the effects of these new technologies on society? . The invisible nature of nanotechnology makes it easier to 'hide' nanotech products, and to invade privacy or carry out procedures that require consent, without the patient's knowledge. This may be particularly pertinent with regard to clinical trials of nanodrugs carried out in developing countries.
Developing country governments will need to tread carefully. The capacity to ensure ethical clinical trials is generally poor in the developed world and introducing health products based on nanotechnology may require an expertise that is lacking . As with other health technologies, there is nothing intrinsically good or bad about nanotechnology. It will depend on how it is used.
In the field of health, advances in nanotechnology are combined with other technologies, including information technology and biotechnology, increasing nanotechnology's potential to 'displace' health measures and systems where regulation has been worked out over many years. One example is the development of computer-controlled molecular tools that may not require the direct intervention of a medical practitioner. Or, nanosensors that measure and store medical information about an individual where issues might arise over the storage, access and use of such information.
Even in the developed world the study of legal, ethical, environmental and equity issues are lagging behind scientific advances in nanotechnology for health. Nanotechnology may not be as advanced in the developing world as in countries like the United Kingdom or the United States, but it's only a matter of time before China and India catch up. Developing nations should not wait until the technology is on their doorstep before figuring out its ethical and societal implications.
This article is part of a spotlight on Nanotechnology for health.