Photodynamic therapy (PDT) uses a light-activated drug to create reactive oxygen species that kill nearby cancer cells. Its use is limited, however, by the low penetration of light into tissue and insufficient accumulation of the photosensitizing drug in tumours. Nanoparticles engineered to deliver the photosensitizer can improve its targeting to tumour sites, but drug accumulation is highly variable between tumours and patients.
A team of scientists in Russia has devised a technique that uses MRI to identify the time of peak photosensitizer accumulation in the tumour, enabling irradiation when the concentration of the drug is at a maximum. The team has now proved the effectiveness of this approach in preclinical tests (Pharmaceutics 10.3390/pharmaceutics10040284).
The researchers — from NUST MISIS, the Moscow Technological University (MIREA) and the Pirogov Russian National Research Medical University — created magnetic nanoparticles (MNPs) loaded with photosensitizer molecules. They evaluated the potential of these hybrid particles for PDT of mice bearing colon carcinoma tumours.
After injecting the mice with the photosensitizer-loaded MNPs, the researchers used MRI to track the particles in the animals’ bloodstream in real time and monitor their accumulation in tumour tissue. MR imaging revealed peak MNP accumulation in the tumours 60 min after injection.
The team verified this finding using atomic emission spectroscopy to measure iron concentration and fluorescence imaging to measure drug accumulation in tumour tissue. Importantly, the photosensitizer delivery profile in tumours was consistent with the MNP accumulation dynamics, suggesting that the two components were delivered to the tumour site together and behaved as a single complex in vivo.
The researchers treated the animals with PDT at different time points after injection and evaluated the resulting tumour growth curves. “We conducted a series of preclinical tests on three groups of mice for 21 days,” explains co-author Maksim Abakumov. “The first group received radiation 30 minutes after injection of the test drug, the second one at 60 minutes, the third after three hours or more.”
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Consistent with the MRI-predicted drug accumulation peak, PDT performed 60 min after injection was more efficient in inhibiting tumour growth than treatment scheduled 30 or 240 min post-injection.
In the first week after treatment, all animals that received PDT demonstrated delayed tumour growth compared with a control group. At day 7, no tumours were found in mice irradiated 30 or 60 min after injection, while tumours in the 240 min group were smaller than those in the control group. From day 10 onwards, however, tumour regrowth was observed in the 240 min group. Animals in the 30 min group exhibited relapse at day 14, but all animals in the 60 min group were tumour-free up to day 22.
“Almost all mice from the second group demonstrated a stop in tumour growth, which proved the correctness of the proposed hypothesis,” says Abakumov.
The researchers concluded that tracking MNP accumulation using MRI can predict peak drug concentration in tumours, enabling scheduling of PDT to maximize anti-tumour response. In the near future, the team plans to start clinical trials of the hybrid nanoparticle.
