The Fascinating World of Nanomedicine: From History to Modern Applications

Over the last few years, you may have heard the term nanomedicine, especially amidst the COVID-19 pandemic and the use of lipid nanoparticle-based mRNA vaccines. Nanomedicine, which applies nanotechnology in the medical field, is revolutionizing how we diagnose, treat, and prevent diseases. But what exactly is nanomedicine, and how did it come to be? In this post, let us take a journey through its history, current applications, and future potential.

The concept of manipulating materials at the nanoscale (one billionth of a meter, or 1/100,000th of the thickness of a human hair) is not as new as it seems. For example, the Lycurgus Cup, a 4th-century Roman artifact, shows different colors depending on the angle of light due to the presence of gold and silver nanoparticles. Similarly, medieval stained glass windows owe their vibrant hues due to gold and silver nanoparticles of varying sizes. These forerunners probably did not realize they were dealing with nanoparticles, yet humanity has been working at the nanoscale for quite some time.

Figure 1: The Lycurgus Cup. Left: when back lit (transmitted light). Right: viewed in reflected light. Images are obtained from Wikipedia

Fast forward to the modern era, the birth of nanotechnology can perhaps be credited to Nobel Laureate Richard Feynman, who first discussed the potential of manipulating molecules at the atomic scale in his famous lecture, “There’s Plenty of Room at the Bottom.” Since then, scientists and engineers have expanded the concept of nanoscale manipulation to applications in electronics, battery technology, and even cosmetics. Researchers began incorporating nanotechnology concepts to solve unmet needs in healthcare, leading to groundbreaking developments in nanomedicine.

Today, nanomedicine is used in various ways to improve healthcare. This blog post will focus on three main aspects of nanomedicine: diagnosis, treatment, and prevention.

Cancer Treatment and Targeted Drug Delivery

One of the most transformative areas of nanomedicine is cancer treatment. Traditional chemotherapy, while powerful, is associated with numerous side effects. For example, the drug doxorubicin is known for its serious side effects ranging from hair loss and nausea to severe heart damage. Nanotechnology was applied to mitigate the potential toxicity while maximizing the treatment efficacy. How? Imagine tiny fat bubbles that contain water inside. A special type of lipids (fat molecule), known as phospholipids, have both hydrophilic parts (can mix in water) and hydrophobic parts (unable to mix in water). Phospholipids naturally assemble into bilayers with the hydrophobic parts facing each other inward and hydrophilic parts facing outward towards aqueous environments. Liposomes, which are formed under such principles, can encapsulate drugs within the inner space to enhance their half-life in circulation (prevent them from breaking down in the watery environment in the body) and allow controlled drug release, minimizing undesired toxicity in healthy cells. For instance, Doxil, the first liposomal version of doxorubicin, was approved by the FDA for advanced ovarian cancer and AIDS-related Kaposi’s sarcoma due to its improved ability to stay in circulation and accumulate at the tumor (1). Other nanoformulations, such as Abraxane (albumin-bound paclitaxel), have been successfully used in clinics for various cancers based on improved pharmacokinetic/dynamic profiles (2).

Another cutting-edge application of nanotechnology in cancer treatment is the development of antibody-drug conjugates (ADCs). ADCs are like a precise lock and key system. They consist of a ligand (e.g., antibodies) that is designed to fit only a specific lock (target cancer cell receptor protein). Once it fits, the lock is opened, and the payload (drug) is released. A prominent example of ADCs in clinics is Kadcyla®, used for HER2-positive breast cancer. Kadcyla consists of Trastuzumab, a HER2-specific antibody, and DM1 (emtansine), a cytotoxic agent that interferes with cell division. Clinical studies show that patients receiving Kadcyla had a 43% improvement in overall survival and an 88% improvement in median progression-free survival compared to those receiving other treatments (3). Additionally, severe side effects were lower in the Kadcyla group (43%) compared to others (59%) (4), demonstrating the improvements offered by ADCs over the conventional treatments.

Imaging and Diagnosis

Nanotechnology also plays a crucial role in improving clinical imaging and diagnostics, enhancing accuracy and efficiency (5). For instance, contrast agents are widely used to improve the quality of images obtained through medical ultrasounds or magnetic resonance imaging (MRI).

Figure 2: Application of nanomedicine in medical imaging and diagnosis. Left: an ultrasound image of patient that received ultrasound enhancing agent. Image is obtained from GEhealthcare.com. Right: an MR Image is obtained from Nguyen K., et al (6).

Medical ultrasound techniques often involve microbubbles, which are tiny gas-filled bubbles under 10 micrometers (1000 times smaller than a millimeter) in size. These microbubbles are formulated by encapsulating gases (e.g. perfluorocarbon) within an outer shell of lipids, albumin, or other proteins, in a manner similar to how lipid nanoparticles are produced. Once in circulation, these microbubbles reflect ultrasound signals, improving image resolution and creating a strong contrast between circulation and surrounding tissues. 

Magnetic Resonance Imaging (MRI) quality can also be enhanced using contrast agents. Ferumoxytol, an iron oxide nanoparticle often used to treat anemia in patients with chronic kidney diseases, also serves as a contrast agent for MRI (5,6). Beyond clinically approved agents, many preclinical developments using metallic nanoparticles like gold nanoparticles (7) or fluorescence-based approaches are being explored to further improve imaging and diagnostics.

Vaccine Development

Lastly, nanotechnology has revolutionized vaccine development, particularly during the COVID-19 pandemic. Traditional vaccines rely on attenuating live viruses in suitable hosts (often chicken eggs or mammalian cells), allowing them to replicate many times in these hosts until they are “weakened” enough to be introduced into healthy individuals without making them sick. The recipient’s immune system then elicits an antiviral immune response against these attenuated viruses, potentially providing lifelong protection. While effective, they often require lengthy production processes, which could be a hurdle when a rapid response is required (8,9).

mRNA vaccines, on the other hand, leverage our immune system to produce certain proteins resembling the virus (e.g., the spike protein for SARS-CoV-2 a.k.a COVID-19), which are non-infectious but can still be recognized by the immune system to mount an effective response. Advances in nanotechnology enable the rapid sequencing of viral targets, identifying the specific genetic codes required to produce proteins of interest. This allows for the customization of target-specific vaccines in a short time frame (8).

Despite the recognized potential of mRNA-based vaccines, their inherent instability, —especially in circulation where they are prone to degradation—often prevents clinical translations. Optimizing lipid compositions addressed these issues by protecting mRNA within the lipid nanoparticles, enabling cellular uptake and intracellular release to induce the production of the protein of interest. These developments culminated in the first human clinical trials of mRNA vaccines in 2013 and their subsequent application during the COVID-19 pandemic.

Conclusion

Nanomedicine represents an incredible fusion of science and healthcare. It offers solutions that are not only innovative but also practical, from targeted cancer treatments and enhanced imaging to life-saving vaccines. As research continues, we can look forward to a future where nanomedicine makes treatments safer, faster, and more effective for everyone. Imagine a world where complex diseases are managed with precision tools as small as a billionth of a meter—that is the promise of nanomedicine.

References

1. Gabizon, A. et al. Prolonged Circulation Time and Enhanced Accumulation in Malignant Exudates of Doxorubicin Encapsulated in Polyethylene-glycol Coated Liposomes1. Cancer Research 54, 987–992 (1994).

2. ABRAXANE for Injectable Suspension (https://www.abraxanepro.com/about-abraxane).

3. Krop, I. E. et al. Trastuzumab emtansine versus treatment of physician’s choice in patients with previously treated HER2-positive metastatic breast cancer (TH3RESA): final overall survival results from a randomised open-label phase 3 trial. The Lancet Oncology 18, 743–754 (2017).

4. KADCYLA Prescribing Information. Genentech, Inc. 2022 (https://www.gene.com/download/pdf/kadcyla_prescribing.pdf).

5. Toth, G. B. et al. Current and potential imaging applications of ferumoxytol for magnetic resonance imaging. Kidney International 92, 47–66 (2017).

6. Nguyen, K.-L. et al. Multicenter Safety and Practice for Off-Label Diagnostic Use of  Ferumoxytol in MRI. Radiology 293, 554–564 (2019).

7. Singh, P. et al. Gold Nanoparticles in Diagnostics and Therapeutics for Human Cancer. International Journal of Molecular Sciences 19, (2018).

8. Wang, X. et al. Fluorescent Probes for Disease Diagnosis. Chem. Rev. 124, 7106–7164 (2024).

9. What Makes an RNA Vaccine Different From a Conventional Vaccine (https://www.pfizer.com/news/articles/what_makes_an_rna_vaccine_different_from_a_conventional_vaccine).