An approach to lessen the adverse effects of intravenous injections of routinely used medical nanoparticles could be provided by a recent study.
Image Credit: University of Colorado Anschutz Medical Campus
On October 5th, 2023, the study appeared in Nature Nanotechnology.
Nanotechnology’s main advantage over conventional medical treatments is its ability to more precisely target tissues, such as cancer cells targeted by chemotherapy. However, when nanoparticles are injected, they can activate part of the immune system called complement.
Dmitri Simberg, PhD, Study Senior Author and Professor, Nanomedicine and Nanosafety, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus
Complement is a set of proteins in the immune system that identify and kill bacteria and viruses, as well as foreign nanoparticles. As a result, immune cells assault nanoparticles, causing symptoms such as shortness of breath, increased heart rate, fever, hypotension, and, in rare circumstances, anaphylactic shock.
Simberg added, “The activation of the immune system after injection of nanoparticles can be challenging to understand and prevent. This research is one step closer to providing a better understanding and a solution for people to receive the benefits of nanoparticles without side effects.”
Mitigating Immune Activation
While considerable success has been achieved in minimizing adverse effects with slow infusion and premedication with steroids and antihistamines, the researchers indicate that a significant proportion of people still have problems.
“The goal is to prevent, avoid and mitigate adverse reactions and immune activation”, Simberg added.
Simberg’s team worked with Michael Holers, MD, of the University of Colorado School of Medicine and the Medical University of South Carolina to investigate the effects of complement inhibitors injected with nanoparticles in animal models.
The study focuses on an intriguing class of complement inhibitors (dubbed “regulators”). The study yielded good results.
Simberg and colleagues discovered that the regulators under investigation efficiently reduced complement activation by nanoparticles in human serum in vitro as well as in animal models. In particular, when given at extremely low concentrations, the regulators totally and safely inhibited complement activation by nanoparticles in the animal models tested.
This is crucial, according to the scientists, because when nanoparticles activate complement, the accompanying immune response might not only induce an unfavorable reaction but also impair the efficacy of nanomedicines.
This study also sheds light on why and how complement regulators could help the body respond more positively to nanoparticles. The researchers discovered that just a small proportion of the billions of nanoparticles injected into the circulation activated complement. Complement regulators began working as soon as nanoparticles activated the complement, preventing immune activation.
Simberg further stated, “These results suggest we have an exciting opportunity to explore how to further optimize the use of regulators with nanoparticles, with the goal of improving the efficacy and tolerability of multiple nanotechnology-based therapeutics and vaccines.”
The next step, according to the researchers, is to test the complement inhibitors with different nanoparticles and disease models to fully grasp the potential of this method, with the ultimate objective of using the discovery in a clinical environment.
The National Cancer Institute and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health funded the research. The authors are entirely responsible for the material, which does not reflect the official views of the National Institutes of Health.
Journal Reference
Li, Y., et al. (2023) Inhibition of acute complement responses towards bolus-injected nanoparticles using targeted short-circulating regulatory proteins. Nature Nanotechnology. doi:10.1038/s41565-023-01514-z.