Nanosized Contrast Agents Could Enhance MR Imaging

Scientists have developed a novel nano-contrast agent (NCA) based around the use of gadolinium (Gd) as a contrast agent in what the researchers called a “self-folding macromolecular drug carrier (SMDC). A research team from Tokyo Institute of Technology (Tokyo Tech), National Institutes for Quantum Science and Technology (QST) and Innovation Center of Nanomedicine (iCONM), led by Associate Professor Yutaka Miura of Tokyo Tech, successfully developed a novel NCA with exceptional performance thanks to an innovative molecular design. Thanks to their small size, low toxicity, and good tumor accumulation and penetration, these complexes represent a leap forward in contrast agents for cancer diagnosis, as well as neutron capture radiotherapy. Their findings were published in the Advanced Science.

They incorporated clinically approved Gd-containing chelates into a polymer chain composed of poly (ethylene glycol) methyl ether acrylate (PEGA) and benzyl acrylate (BZA). Since the polymer contained both hydrophilic and hydrophobic segments, it quickly folded itself into a small capsule-like shape when immersed in water, with the hydrophobic segments at the core and the hydrophilic segments at the outer shell.

Using this approach, the researchers could produce SMDC-Gds molecules smaller than 10 nanometers in diameter. Through experiments in mice with colon cancer, they verified that these NCAs not only accumulated better in tumors, but that they were also promptly eliminated from the bloodstream, leading to enhanced MRI performance without toxic effects. “the high accumulation in tumor while quick blood clearance profile of SMDC-Gds allows for the increase in the tumor-to-major organ accumulation ratios as well as minimizing the unnecessary deposition of Gds,” explains Prof Miura.

Moreover, the team also demonstrated a novel effect that puts SMDC-Gds ahead of existing Gd-chelates. Ideally, the motion of Gd ions should be minimal so that their influence on nearby hydrogen ions is steady and prolonged. In the proposed molecular design, the core/shell structure creates a ‘crowded’ molecular environment that suppresses not only the rotation, but also the segmental and internal motions of Gd ions. The resulting effect is a stronger contrast in MRI images, which will allow for use of alternative elements with safer profiles not only in patients but also environment in future.

The applications of SMDC-Gds extend beyond MRI. These compounds can be used in neutron capture therapy (NCT), a promising targeted radiotherapy technique in which Gds capture neutrons and release high energy radiations, killing nearby cancer cells. Experiments in mice revealed that NCT following repeated SMDC-Gd injection led to greatly suppressed tumor growth. The team believes the reason for this was the selective accumulation and deep penetration of SMDC-Gds into tumor tissues.

Collectively, the researchers’ collaborative efforts to achieve these findings underscore the potential of SMDCs not only for better MRI diagnostics, but also as effective tools for treating cancer and other diseases. “This study presents further possibilities for exploiting drug delivery using various therapeutic cargos, and we are currently investigating the development of such SMDC systems,” concludes a hopeful Prof Miura.