A nanoscale arsenal

[First published on 11 December 2020 ; Nature India Special Issue: COVID-19 Engineering Solutions]

The world has made tremendous progress in science, technology and medicine since the last epidemic of Spanish flu a century ago; still, our ill-preparedness for a pandemic has forced us to look for better alternatives and strategies. We have already faced several viral outbreaks such as Zika virus, Ebola virus, and swine flu, as well as the long fight against tuberculosis (TB), HIV, and hepatitis C (HCV) in the last century. These experiences have taught us that although microbes and humans have co-existed and interacted with each other, we must be mindful of risk, and that no matter how aware and prepared we are, we must face the unexpected and develop broad-spectrum strategies to emerging microbial threats.

Can nanotechnology provide fast, accurate and cost-effective diagnostic tools?

The COVID-19 challenge comes from the fact that asymptomatic infected people may be a significant source of spread, as with TB, HCV, or even HIV, where early and accurate diagnosis at initial stages of the infection can lead to better management and treatment.

Let us understand this by comparing HIV and COVID-19. AIDS caused by HIV is one of the most significant challenges of this century. An estimated 690,000 people died from AIDS-related illnesses in 2019. In the absence of any groundbreaking treatment, early diagnosis remains key to prolonging life. In countries such as India, with a huge population, significant poverty, and sub-standard healthcare system, the challenges are more critical.

Even after 40 years of research, ELISA based diagnosis (enzyme-linked immunosorbent assay), which has several limitations, is still the gold standard. Biosensors based on nanotechnology are regarded as a great hope to overcome these challenges. Their benefit comes through their unique properties, such as small size (1—100 nm, matching these microbes), shape (can be designed to mimic the micro surface), ease of function (chemically tailorable), high sensitivity (high surface to volume ratio), and robust structure. Several nano-based sensors are already being developed and tested based on biochemical, electrochemical, electromagnetic conjugated with molecular technologies for HIV biomarker detection.

COVID-19 was effectively controlled in some countries, such as South Korea and Hong Kong, due to robust testing. Early in the outbreak, governments across the world used rapid COVID-19 antibody tests to diagnose infection, but many failed to detect the stage of infection. Later, more evolved tests using nanotechnology (colloidal gold method) that can detect very low viral loads with high sensitivity were developed, which helped in controlling the spread of infection and suitable treatment paths. Nanotechnology is poised to revolutionize the diagnosis of pathogens by enabling safer, faster, reliable, cost-effective and sensitive nanodevices and nanoprobes for microbial detection and screening.

The tools of prevention

Researchers have been working constantly to find a vaccine — and nanotechnology is among their strongest tools. To outline the process: viral or bacterial infections generate an immune response (antibodies) by recognizing virus/ bacteria proteins on the surface (antigens) that neutralize these pathogens. Blood therapyusing plasma of recovered patients (used in India for COVID-19 treatment) is based on this concept, where the transfused plasma contains high levels of virus-neutralizing antibodies.

Vaccine development involves the same logic where a viral/bacterial mimicking immunogenic material is administered to generate a strong immune response without causing disease symptoms. The immune response of a potent vaccine depends on antigen stability, delivery and presentation. Over the last decade, nanomaterial-based vaccines have provided compelling advantages in vaccine development by increasing antigen stability, multivalent presentation to B cells leading to strong and enhanced immune response. Several nanoparticles, including self-assembled protein nanoparticles, organic nanoparticles, inorganic nanoparticles, and liposomes have been explored to generate an immune response.

The earliest example of nanoparticle-based vaccines used ferritin for developing influenza, HIV, hepatitis B and hepatitis C virus vaccines. In the case of COVID-19, the development of a modular nanoparticle-based vaccine, where the antigen within is interchangable, showed recent signs of progress for rapid vaccine development. It also showed that the vaccine developed a 10-fold higher antibody titre when used at five times less dosage than a soluble antigen. The results were validated in mice, and there are plans for human clinical trials in early 2021. Looking ahead, biomimetic nanomaterials hold promise for fighting infectious diseases, and could lead to the development of next-generation antiviral and antibacterial vaccines and therapies.

Antiviral and antibacterial therapy

In heavily populated countries such as India, infectious diseases due to bacteria, viruses, and parasites pose a serious public health threat Nanomedicine, with its unique capabilities, offers a modular and broad-spectrum antiviral and antibacterial therapeutic concept. We need to channel efforts effectively to develop targeted therapies against a broad spectrum of pathogens, rather than a single target whether it is COVID-19, HIV or hepatitis C.

Targeting strategies through broad-spectrum microbial and host targeting will provide multilateral solutions to current, as well as emerging microbial threats. Regarding targets, although each virus or bacteria has a unique structure, they share some similarities, which need to be identified and targeted. Nanomaterials can carry multitargeted entities, thus making it easier to target a broad spectrum of microbes through direct microbe targeting or stopping host cells or both.

A few examples using this approach include nitric oxide-releasing nano antibiotics, that can target bacterial cells through multiple paths. Other examples include interferon-lambda (IFN-λ), nanomaterial-enhanced replication inhibitors, membrane inhibitors and so on. Also, the therapies can be designed and delivered in a precise manner to have higher efficiency, specificity and sensitivity. It is important to understand that to make these concepts work needs a coordinated effort of biologists, engineers, material scientists and the private sector industries

Pre-emptively inactivating pathogens

Though treatment through antiviral, antimicrobial therapies or vaccines is the first-line approach to treat these microbial infections, rendering these infectious agents inactive before entering the host will play a major role in combating future pandemics.

Contaminated surfaces in public spaces are a major conduit for the uncontrolled outbreak of these infectious diseases. Nanoformulation based coatings that can be antimicrobial, or release antimicrobial agents on demand, have provided a new perspective to fight the pandemic causing agents.

These systems can be smart and responsive, releasing antimicrobial agents upon stimuli such as touch, change in temperature, or rubbing, making them an efficient tool to fight the spread of infection. Nanomaterial based PPE kits, nanoengineered masks for healthcare workers and the general public will provide additional comfortable, resistant, and safer means of protection against these microbes.

Technical Institutes in India, including IIT Kanpur, have exploited nanotechnology to develop nano-based products such as masks and PPE kits, which have been praised. However, these scientific efforts require effective coordination and collaboration among various stakeholders from government agencies to private partners to be successful.

Lessons learned and the way ahead

Nanotechnology can be a great weapon to fight future pandemics on various fronts. We have to find innovative solutions using this tool to track, target and eliminate the threat of these deadly microbes. Other technologies will complement nanotechnology to develop an innovative engineering solution in this global fight against existing as well as emerging microbial threats. We see an optimistic future where a coordinated effort from scientists of varying backgrounds will help to control some of the biggest problems of medical science, including microbial infections.

*Endowed chair professor of Bioengineering at Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur ( BSBE, IITK). **PhD and Post Doctoral Researcher at BSBE, IITK.