Activated gold helps visualise drug movement in the body

Tracking targeted drug delivery is often a challenge due to limitations in current imaging techniques. Now, Japanese researchers have developed a technique that enables direct and highly sensitive tracking of gold nanoparticles (AuNPs) inside the body, which could revolutionise cancer drug delivery.

Gold nanoparticles (AuNPs) are tiny gold particles of 1–100 nm and have unique chemical and biological properties. Due to their potential to accumulate in tumours, they have emerged as promising drug carriers for cancer therapy and targeted drug delivery. However, tracking the movement of these nanoparticles in the body has been a major challenge. Traditional imaging methods often involve tracers like fluorescent dyes and radioisotopes, which give limited visualisation and inaccurate results due to detachment from AuNPs.

Researchers from Waseda University have now introduced a new imaging technique that uses neutron activation to transform stable gold into a radioisotope of gold and enables long-term tracking of the AuNPs within the body. The study was led by Nanase Koshikawa and Professor Jun Kataoka from Waseda University, in collaboration with Osaka University and Kyoto University. Their findings were published in the journal Applied Physics Letters.

“Traditional imaging methods involve external tracers, which may detach during circulation,” Koshikawa said. “To overcome this limitation, we directly altered the AuNPs, making them detectable via X-rays and gamma rays without the use of external tracers.”

For activation of the AuNPs, the researchers irradiated the stable gold nanoparticles with neutrons, converting the stable (¹⁹⁷Au) to radioactive (¹⁹⁸Au). The radioactive ¹⁹⁸Au emits gamma rays, which are detectable from outside the body.

“Activation of atoms through particle irradiation is a technique that directly alters the material,” Kataoka explained. “The altered elements are sometimes unstable and emit X-rays and gamma rays that make the material visible from outside the body. This does not change the atomic number, and thus the chemical properties of the element are preserved.”

The researchers further confirmed the tracking of these radioactive AuNPs by injecting them into tumour-bearing mice and visualising them using a special imaging system.

Additionally, the study demonstrated their imaging technique for drug delivery of ²¹¹At, a radio-therapeutic drug used in targeted cancer therapy. ²¹¹At emits alpha particles and X-rays, which are detectable for a shorter duration due to a shorter half-life. The researchers labelled ²¹¹At with the radioactive AuNPs, forming ²¹¹At-labeled (¹⁹⁸Au) AuNPs. This approach provided long-term imaging of the drug due to the longer half-life (2.7 days) of ¹⁹⁸Au, overcoming the limitations of the short half-life of ²¹¹At.

“²¹¹At has a half-life of only 7.2 hours, and hence its emitted X-rays disappear within two days, but with the (¹⁹⁸Au) AuNPs labelling, we were able to track the drug’s distribution for up to five days using gamma rays from ¹⁹⁸Au, which has a longer half-life of 2.7 days,” said co-author Atsushi Toyoshima, from the Institute for Radiation Sciences at Osaka University.

The study could lead to major advancements in drug delivery systems, with the direct tracking of AuNPs inside the body potentially paving the way for more effective cancer treatments with precise monitoring of drug distribution. The study could also open new possibilities for real-time pharmacokinetic studies, ensuring improved drug safety and efficacy.

“AuNPs are being actively researched for medical applications,” said co-author Hiroki Kato, from the Institute for Radiation Sciences. “We developed a simple and scalable technique for tracking AuNPs that could significantly advance nanomedicine while driving the optimisation of gold-based nanomaterials.”

Co-author Assistant Professor Yuichiro Kadonaga, also from the Institute for Radiation Sciences, added, “We plan to enhance the imaging resolution and extend this technique to various nanoparticle-based systems. By further refining neutron activation imaging, we aim to make drug monitoring a clinical reality, potentially revolutionising the field of imaging technologies.”

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