Big Problems, Small Solutions: Exploring Extracellular Vesicles as Biomarkers of Idiopathic Lung Disease

Dr. Anjali Singh Interviews Dr. Nagarjun Konduru, Assistant Professor at The University of Texas Health Science Center at Tyler (UT Health)

50 million people across the world are struggling with occupational or workplace related lung diseases, says the World Health Organization, occasionally causing death and disability1. Air-borne nanoparticles (< 100nm) are one of the leading causes of occupational and environmental lung diseases. These nanoparticles frequently interact with biomolecules within the lung tissue to form unique complexes causing a mysterious biodistribution fate of nanoparticles in the human body. We got in touch in with Dr. Nagarjun Konduru, Assistant Professor at The University of Texas Health Science Center at Tyler (UT Health), who has been actively working in the field of nanotoxicology for the last 13 years. During his post-doctoral training under Dr. Joseph Brain at Harvard-NIEHS Nanosafety Research Center at Harvard T.H. Chan School of Public Health, Dr. Konduru worked on the development of predictive in vitro and in vivo models for determining the pharmacokinetic fate of Engineered Nanoparticle (ENM) based on the ‘corona’ formation on the surface of nanoparticles upon their interaction with proteins of the alveolar lining fluid. “Key questions like what are the determinants of the translocation of these complexes into different organs”, cites Dr. Konduru, led him to explore fundamental proteins found in the alveolar lining fluid which could have a potential role in the biological fate of ENMs2.

Dr. Nagarjun Konduru, University of Texas

Dr. Nagarjun Konduru and the team at The University of Texas Health Science Center at Tyler (UT Health)

Extracellular vesicles (EVs) have evolved as specific pathologic signatures bound to out-perform other predictive and diagnostic clinical markers. “During the course of conducting nanotoxicological and biokinetic studies, we found some very interesting data from the exosome profiles”, recalls Dr. Konduru. The broncho-alveolar (BAL) fluid EV profile of animal models used in Dr. Konduru’s lab exhibited a unique molecular signature with each type of the ENM exposure. Further analysis by detailed proteomic, micro-RNA and other unique signature profiling studies made EVs strong candidates as exposure biomarkers for individual contaminants giving a more real-time picture of exact body burden. “These exciting findings have led us to a clinical project on EVs as diagnostic biomarkers of Idiopathic Pulmonary Fibrosis (IPF)”, says Dr. Konduru. The main hurdle with IPF diagnosis is that it’s a disease of diagnosis of exclusion of other interstitial lung diseases that encouraged Dr. Konduru to investigate if EVs can distinguish IPF from IPF-mimickers. His research team is using Izon’s Size Exclusion Chromatography qEV columns to separate pure volumes of EV from patient plasma, urine and BAL fluid samples. Ecstatic with the results obtained, Dr. Konduru remarks, “we could successfully get unique signatures for IPF using qEV columns differentiating it from IPF-mimickers”. He further adds, “when compared to other methods, the exosomes isolated are purer without any traces of lipoproteins and the AFC is an overall cost-effective technique to use with large number of samples”.

When asked how the lab characterizes the isolated EVs, Dr. Konduru replies, “I was kind of fascinated and attracted by the TRPS output which gives us accurate single particle measurements and true particle concentration as well as zeta potential”.

While it is a well-known fact that the field of EVs is relatively new and still in its infancy, no standard predictive or diagnostic biomarkers currently exist for IPF. Commenting on the present-day scenario, Dr. Konduru signs off saying, “true EV surface markers for different sub-populations need normalization, there’s still a long way to go”.

References

  1. Forum of International Respiratory Societies & European Respiratory Society. The global impact of respiratory disease. (2017).
  2. Konduru, N. V. et al. Protein corona: implications for nanoparticle interactions with pulmonary cells. Part. Fibre Toxicol. 14, 42 (2017).