The COVID-19 pandemic has brought about devastation worldwide and has become one of the most challenging global health threats in modern history. Advances in nanotechnology have come to the rescue in the form of rapid diagnostic tests and, perhaps more importantly, swiftly developed vaccines against SARS-CoV-2. At the same time, numerous non-technical issues have complicated the deployment of these novel technologies and have brought to the fore the urgent need to incorporate ethical, environmental, economic, legal, social and cultural (E3LSC) considerations in the development and implementation of nanotechnological solutions for global health challenges.

In this Commentary, we use the development and implementation of COVID-19 related nanovaccines as windows to the broader field of the application of nanotechnology to global health. We consider several E3LSC challenges related to the concept of ‘nanoequity’, and we suggest some strategies to address these challenges.

Medical nanotechnologies for the developing world

In 2005, we identified the ten nanotechnology applications most relevant to the developing world and correlated them with the Millennium Development Goals1. Crucially, three of these applications (disease diagnosis and screening, drug delivery systems and health monitoring) are critical for global health; several of the other categories in this list, such as water treatment and remediation, agricultural productivity enhancement, and air pollution and remediation, are directly relevant to addressing global health issues.

The wide range of nanomedical applications for global health can impact nearly every medical specialty and can improve the quality of life of people in low- and middle-income countries (LMICs), extending life expectancies, and reducing overall costs of healthcare2. The convergence of nanotechnology with other advanced technologies has catalysed the development of thermostable, single-dose, needle-free vaccines with increased shelf life that reduce required dosages and transportation costs; easy to use, highly sensitive and specific, robust, portable handheld point-of-care diagnostic systems; and novel delivery systems for the slow and targeted release of medications that improve specificity and decrease side effects2,3,4. Table 1 lists representative examples of nanotechnology-related projects funded by the Grand Challenges in Global Health Initiative (https://gcgh.grandchallenges.org/grants).

Table 1 Examples of nanotechnology-related projects in the Grand Challenges in Global Health Initiative
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To meet the life-threatening challenges of the current pandemic, the scientific community has responded with unprecedented speed. Nanomedical advances have borne fruit as at least three COVID-19 vaccines5,6. The first two vaccines licenced for clinical use in humans (developed by Pfizer/BioNTech7 and Moderna8) use lipid nanoparticles to cage, stabilize and transport mRNA molecules, while the Novavax vaccine9 uses a proprietary recombinant protein nanoparticle technology platform to generate antigens derived from the SARS-CoV-2 spike protein. Future developments in nanotechnology could enable the addition of desirable features to these vaccines such as thermostability (ideal for places in LMICs with no adequate drug storage capabilities and distribution networks), needle-free single dose application and increased safety and efficacy2,5.

‘Nanoequity’ and the E3LSC challenges

However, addressing global health challenges is not simply a matter of identifying technical problems and developing technological solutions to overcome them. The excitement over novel technologies can hinder serious examination of the social and cultural contexts in which health care is delivered, a crucial component of the success of any health intervention. As is the case with other nanomedical technologies, the development and implementation of the COVID-19 nanovaccines have materialized in specific social and cultural settings and have demanded making complex moral decisions transcending the technical dimension of these advances. In particular, one of the most severe moral failures in the implementation of measures to control the current pandemic has been the lack of equity in the distribution and application of the COVID-19 nanovaccines. Not only has the roll-out of the vaccines favoured wealthy populations and countries, but industrialized nations have hoarded the pre-ordered doses of the vaccine to the detriment of the vast majority of people living in the developing world10,11. As Dr Tedros Adhanom Ghebreyesus, Director-General of the World Health Organization (WHO), has stated, “The world is on the brink of a catastrophic moral failure and the price of this failure will be paid with lives and livelihoods in the world’s poorest countries”12.

This is a glaring example of the lack of equity that can characterize the use of nanomedical advances to address global health issues. If we accept the premise that equity is critical for global health, and that it should be the guiding principle in the pursuit of improving the quality of life for people worldwide13, then this absence of ‘nanoequity’ is beyond unacceptable. It also creates numerous risks that threaten to destabilize the world. Misusing or limiting access to medical nanotechnologies could create a ‘nano-divide’ between wealthy and poor populations and countries, exacerbating existing differences in health outcomes and resource and power disparities4,14,15,16,17. Moreover, all aspects of medical nanotechnology research, development and innovation (RDI) may come under the control of powerful interests, and market forces may bias the development of medical nanoapplications and nanoproducts towards the wants of the wealthy and not towards the needs of the poor. If markets and commercial prospects, instead of local needs, drive medical nanotechnology RDI, risks (financial or otherwise) can be externalized onto vulnerable populations14,16,17.

Lack of equity in the development and implementation of medical nanotechnologies may manifest in other ways. For example, the COVID-19 nanovaccines require storage at very low temperatures. But these potentially life-saving innovations may be rendered ineffective by the lack of operational ‘cold chains’ in many developing countries. Thus, medical nanotechnologies may be unsuitable to LMICs if developers in high-income countries (HICs) fail to consider infrastructural barriers such as unreliable or non-existent clean water supplies, minimally trained personnel, poor leadership and a lack of coordination between different levels of the supply chain3,18. Nanomedical products designed for use in HICs may not function properly in LMICs due to humidity, heat or dust. Diagnostic systems requiring single-use cartridges only available through the equipment manufacturer, or needing costly regular maintenance and repair, may not be suitable to LMICs3. It stands to reason that medical nanotechnologies should be developed with awareness of the target context in which they will be used, even if doing so reduces their versatility. Incorporating local expertise in the design of these technologies, and encouraging their development within LMICs, would seem a reasonable way to address these challenges.

The promise of COVID-19 nanovaccines has been clouded by the fear19 that multinational pharmaceutical corporations will be reluctant to share their intellectual property rights with LMICs outside of the scope of strict commercial transactions. Human Rights Watch has called for urgent waivers of intellectual property rules for coronavirus vaccine development20. Aggressive patenting of nanomedical products by HICs, broad and restrictive patents and trade barriers risk consolidating ownership of medical nanotechnologies in the industrialized world. This could stifle domestic RDI in LMICs, reducing their ability to develop applications that could benefit vulnerable populations; it could also force developing countries to pay exorbitant fees for the use of nanotechnologies created and patented in the industrialized world4,16. Moreover, if most patents related to medical nanotechnology focus on medical conditions common in rich countries at the expense of neglected diseases prevalent in LMICs, vulnerable populations in these countries will be at a severe disadvantage to address their most pressing medical concerns4. To make matters worse, regulatory frameworks in LMICs may lack the nimbleness and flexibility that novel medical nanotechnologies demand. Given how devastating the pandemic has been for vulnerable populations in poor countries, there is a compelling argument for companies to reduce the stringency with which they enforce their intellectual property protection.

Inadequate sensitivity to the social and cultural dimensions of medical nanotechnologies may be particularly harmful to vulnerable individuals in LMICs. They may be used as experimental subjects for nanomedicine clinical trials, receiving none of the benefits of the research projects21. Their ideas about the definitions and limits of identity, normalcy, disability, health and disease, and their conceptions about what is and is not part of the natural human body, may be disregarded in their government’s pursuit of ‘keeping up’ with innovations in nanotechnology4. Rejection of unfamiliar novel nanomedical technologies due to clashes with local beliefs and experience may be compounded by fear of being tested or treated for stigmatized diseases such as HIV/AIDS18. Individuals in LMICs without access to nanobiomedical advances or without the desire to take advantage of such technologies may be discriminated against4.

LMICs could bear a disproportionate burden of the negative environmental effects of medical nanomaterials and nanoproducts, especially in the absence of proper evaluations of their complete life cycles. The developing world could become the dumping ground of unwanted, low-quality or potentially toxic medical nanoproducts from industrialized nations. Furthermore, healthcare workers in LMICs may be particularly vulnerable to the negative effects of medical nanotechnologies: they may be exposed to highly toxic nanomaterials, and they risk being replaced by advanced nanodevices4,22.

It is not surprising that many vulnerable populations in LMICs have reacted with fear and apprehension towards the COVID-19 nanovaccines, especially in countries that have suffered the ruthlessness of colonialism. Inequities in the development and implementation of these and other medical nanotechnologies may kindle such mistrust and cause considerable damage to public health in LMICs. For example, absence of trust in diagnostic nanodevices may lead to lack of compliance with negative results and to the consequent adverse effects of unnecessary overmedication18.

The possible ways forward

The global community has the ethical responsibility to harness promising advances in nanomedicine to mitigate the most pressing health needs of vulnerable populations, especially in the developing world, while simultaneously preventing a nano-divide2,4. In the case of the COVID-19 vaccines, WHO has issued a call to action23 to all countries to work “…in solidarity — and in each of their best interests — to ensure that within the first 100 days of [2021], vaccination of health workers and older people [is] underway in all countries.” Progress in this laudable goal is being tracked in real time (https://pandem-ic.com/vaccine-equity-tracker). Moreover, several developing countries have demanded that the World Trade Organization exempt member countries from enforcing some patents, trade secrets or pharmaceutical monopolies under the organization’s agreement on trade-related intellectual property rights (TRIPs)24. This clamour has been strongly supported by the WHO Director General25.

Broad vaccination against COVID-19 worldwide could be fulfilled by supporting the Access to COVID-19 Tools (ACT) Accelerator26 and its vaccine pillar, COVAX (https://www.who.int/initiatives/act-accelerator/covax). The ACT Accelerator is a ground-breaking global collaboration that aims to accelerate the development, production and equitable access to COVID-19 tests, treatments and vaccines. COVAX, co-led by the Global Alliance for Vaccines and Immunisation (GAVI), the Coalition for Epidemic Preparedness Innovations (CEPI) and WHO, is a global initiative aimed at equitable access to COVID-19 vaccines.

In the spirit of these initiatives, we present in Table 2 a list of strategies that can potentially address both the lack of ‘nanoequity’ in the development and implementation of medical nanotechnologies, and several related E3LSC challenges, with the aim of facilitating the judicious development and implementation of medical nanotechnologies in LMICs. Some of these strategies could be incorporated into our 2005 proposal of issuing a series of Grand Challenges in Nanotechnology1,4,27,28, now with an urgent focus on global health.

Table 2 Strategies addressing ‘nanoequity’ risks and challenges in the development and implementation of medical nanotechnologies for global health
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In summary, advances in nanomedicine have life-saving potential for vulnerable populations in the developing world. However, their design, development and implementation must be guided by equity as both a moral principle and a policy goal.

A broad search for examples of the successful, sustained and sustainable implementation in LMICs of medical nanotechnologies designed to address global health challenges led to several innovations that, while promising29,30,31, still have not completed the translation “from the lab to the village”32. In other words, their long-term, continued use in the developing world demands overcoming many of the E3LSC challenges mentioned in this commentary.

The successful application of nanomedical technologies demands serious attention to the social and cultural contexts in which they will be applied, and requires understanding that, as exciting as they may be, technological solutions are deeply embedded and influenced by the milieu from which they arise and whose systemic inequities they can perpetuate.