Big things come in nanoscopic packages

8 April 2016

Imagine a world where advertisements for medication could be just two minutes long instead of five. Dr Jonathan Choi wants to do away with the fine print of side effects and complications to do just that, and is helping to revolutionise medicine on the way.

As an assistant professor of Electronic Engineering at The Chinese University of Hong Kong, Choi operates in a small but multi-hyphenate corner of science, broadly dubbed bionanotechnology, using nanotechnology to address biological problems, and nanomedicine in particular. 

His current research can be classified into three broad channels: engineering new materials, composed of molecules and nanoparticles; studying how new bionanomaterials interact with living systems; and evaluating the translational potential of nanoparticles as targeted medicine.

Nanotechnology in the body

Nanoparticles typically measure at just 1-100 nanometres across, too small to be seen by the naked eye but substantially bigger than individual molecules of DNA and glucose. Keeping true to the adage that good things come in small packages, Choi says that nanoparticles can be used to package many components into a bigger construct to improve their pharmacological properties. 

To contextualise his research, Choi focuses on the use of nanoparticles as carriers for drugs, or robots within the body to find biostructural issues to aid in treating and diagnosing disease. This requires understanding and testing how manufactured nanoparticles travel in the body and enter cells, as well as their wider impact on tissues, cells, and other organs. 

A key challenge in current medicine and treatment techniques is controlling interactions between drugs and the body, what we usually term side effects. 

Understanding the nano-bio interactions at target sites helps design nanoparticles that can treat specific organs or issues, bypassing the bottlenecks and limitations of traditional medical options. Lacking this targeted drop delivery, most medicines impact the whole body, such as in the case of anti-inflammatories, steroids, and chemotherapy. This wide diffusion means that some organs may not get the full effect of medication, whereas others, such as the more porous liver and spleen, get too much.

Working together

Choi keeps an open mind due to the applied nature of his research, but it is mostly driven by the kind of diseases commonly recurring in partner medical schools and what collaborators have in mind. 

“It’s a common pitfall for scientists—we make many interesting nanoparticles for hypothetical use, and medical and bioengineers make others without fully knowing how they would do their jobs. Working together, my medical colleagues can provide a specific question that I can address as an engineer, hopefully ending in a mechanistically superior, targeted nanoparticle,” says Choi. 

 While tumours seem to be the most obvious fit for Choi’s work, the field of cancer medicine, even from a nanotechnology view, tends to be overcrowded.

The unique behaviours of individual cancers are also not best suited to the current stage of nanoparticle research. 

“We are still trying to understand so many kinds of moving parts,” he explains, “the size and charge of nanoparticles, the host cell type, delivery routes, the basic chemistry of certain drugs packaged into nanoparticle delivery.” 

Basic testing on the liver and spleen, whose cell structures allow much easier access to nanoparticles, is a first step to understanding nanoparticles’ movement as well as how to better direct their impact away from specific organs.

Using nanoparticles as a tool for better diagnostic imaging as well as treatment vehicles is another possibility currently being probed, expanding on ongoing research on nanoparticles’ reactions with cell receptors. “Early detection and a better understanding of individual cases could greatly boost the efficacy and outcome of treatment for major diseases,” Choi muses.

Nanoparticle targeting

Perfecting nanoparticles’ homing device is a central research issue, and one Choi is especially drawn to. As a PhD student, he came up with a way to direct nanoparticles to the kidney and stay there by tuning their hydrodynamic size, the first time it had been done. 

“It was a long process of studying the kidney and finding the right size for nanoparticles to have them go directly there and stick after injection,” he notes, and while every organ and cell responds to nanoparticles differently, this basis was vital in piquing his interest as a researcher. While the foundation is the same, finding just the right combination of nanoparticle and drug for specific cells and organs is a finely detailed process, and Choi is keen to develop this further.

In recognition of his work, Choi recently won a Croucher Innovation Award, which celebrates talented scientists in the formative stage of their careers. 

The $5,000,000 prize is designed to support awardees’ advancement of expertise, new research, and contribution to the development of education and research in Hong Kong. Choi plans to continue to engineer novel nanoparticle-based approaches for drug delivery, and specifically address options for atherosclerosis and renal fibrosis. 

“This is a great gift for the university and our research team,” Choi said. “We have so many wonderfully talented PhD students and postdoctoral fellows, and being able to better collaborate with other faculties will give them and our research a unique edge.”

The power of curiosity

Choi credits his interest in science and academic path to teachers who taught him to question intelligently. Most young people are drawn to science as a way of understanding big questions of the world, but sustaining that curiosity can be a challenge. 

“In secondary school, I had a wonderful chemistry teacher who really showed me how to keep asking those questions,” Choi remembers. “When he taught us about atoms, he showed us the typical electron diagram, and once we memorised it, he asked us how we actually knew those electrons existed—that is, how could we as passive learners from textbooks definitely tell whether the science is correct without actively validating the conclusions via experimentation.” 

Finding that chemistry held the most adventure, Choi chose to study chemical engineering. Adding engineering allowed him to apply basic chemistry principles and physics to solving interesting biology problems, ultimately leading to a bionanotechnology focus. 

After completing his doctoral studies, the lure of pharmaceutical or management consultancy companies at first seemed bright. At the urging of another professor, Choi decided to hone his research expertise in academia through a postdoctoral post at Northwestern as a Croucher fellow. There, he had the opportunity to serve as a mentor himself, supervising younger researchers and discussing biomedical questions with them. 

“As an assistant professor now, I can ask all the questions I want and test out new ideas, while hopefully also guiding new creative minds,” Choi says.

As nanoparticle synthesis itself is no longer a technical obstacle in the field of nanomedicine, Choi and his colleagues are looking forward at new questions, though he notes that research on fundamental biological interactions will be ongoing. “Modern life brings serious but scientifically interesting problems, particularly through chronic diseases,” he says. “Chronic issues significantly reduce quality of living and the medicines to treat them can cause a host of problems themselves.” 

Bio-nanotechnology is key to finding better treatment options and personalised medicine. This opens up more opportunities for interdisciplinary collaboration, requiring the participation of not only chemists or material scientists to prepare nanoparticles, but also life scientists and physicians to understand their biological behavior. 

“It is an exciting time to be a researcher in this field,” Choi notes, “You never know when you’ll be able to connect the dots between different disciplines to come up with a bold new idea that will change everything.”

Dr Jonathan Choi received his undergraduate and master’s degree in chemical engineering from Stanford University in 2005 and 2006, and went on to the California Institute for Technology for his doctoral work in chemical engineering. From 2011 to 2013, he was a Croucher postdoctoral fellow at Northwestern University, studying the movement of oligonucleotide-based nanostructures, and was just named a Croucher Innovation Award winner for 2016. He is currently an Assistant Professor of Biomedical Engineering in the Department of Electronic Engineering at The Chinese University of Hong Kong. 

To view Choi's personal Croucher profile, please click here.