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New hope for the early diagnosis and treatment of glioma
24 Nov 2022
Glioma is the most common form of malignant primary brain tumour, and it accounts for about one-third of all brain tumours. Yet there are limitations in the existing diagnostic and therapeutic approaches. A HKBU collaborative research team has synthesised a nanoparticle named TRZD that can emit persistent luminescence for the diagnostic imaging of glioma tissues in vivo and inhibits the growth of tumour cells by aiding the targeted delivery of chemotherapy drugs. The research results have been published in Science Advances, an international scientific journal.
Novel nanoparticle helps diagnostic imaging and drug application
Magnetic resonance imaging (MRI) is commonly used to diagnose glioma, but the technology is not highly sensitive. Cerebellar glioma, a relatively rare brain tumour, is even harder to detect with MRI. Doxorubicin, a chemotherapy agent, is an effective treatment for glioma. However, its application may also damage normal cells, and it is associated with a range of side effects.
A research team co-led by Dr Wang Yi, Assistant Professor of the Department of Chemistry at HKBU, and Professor Law Ga-lai, Professor of the Department of Applied Biology and Chemical Technology at The Hong Kong Polytechnic University, has synthesised a novel near-infrared (NIR) persistent luminescence nanoparticle called TRZD, which can play a dual role in diagnostic imaging and as a drug carrier for glioma.
TRZD is a combination of nanoparticles, and it has the characteristic of emitting NIR persistent luminescence after excitation with ultraviolet (UV) light. Loaded with the mesoporous structure of silica, TRZD is a good carrier of doxorubicin particles. Its surface is coated with red blood cell membranes to increase its stability, and it is embedded with T7 peptides, which have a strong affinity for transferrin receptors which are abundant on the surface of tumour cells. T7 peptides can also facilitate TRZD’s penetration through the blood-brain barrier.
A promising agent for accurate diagnosis of glioma
The research team evaluated the efficacy of TRZ (i.e. TRZD without doxorubicin) in diagnostic imaging for glioma with mice whose cerebrum and cerebellum were injected with tumour tissues. TRZ particles were first excited by UV light to initiate luminescence. The mice were then treated with TRZ. In the following 24 hours, TRZ luminescence was detected at the tumour sites of the mice.
Dr Wang says: “Our experiment suggests that TRZ is a promising bioimaging agent for the diagnosis of glioma. It was observed that TRZ’s luminescence can be detected in tumour cells in both the cerebrum and cerebellum regions of the brain, which is an encouraging result because glioma in the cerebellum region is difficult to detect with existing diagnostic methods. As a result, TRZ offers new hope for the timely and accurate diagnosis of glioma.”
Inhibiting the growth of glioma
The research team further evaluated the anti-tumour efficacy of TRZD with a mouse model. After applying TRZD for 15 days, the average diameter of the tumours in the mice was reduced to 1 mm. The mice also survived 20 days longer on average compared to the control group, who had not received TRZD. Besides, cell death was observed in the tumour region but not in normal brain tissue.
Dr Wang says: “The experimental results indicate that TRZD’s therapeutic effect on glioma has good selectivity, because doxorubicin is brought specifically to tumour cells due to T7 peptide’s strong affinity with tumour cells’ surface receptors and its ability to penetrate the blood-brain barrier. As a result, doxorubicin can be applied in a more targeted manner, and hopefully its side effects can be minimised with a reduced drug dosage.
“We concluded that TRZD demonstrates promising potential, and it could be developed into a new generation of anti-glioma drugs that can perform the dual function of diagnosis and treatment. It also offers hope for the development of treatment protocols for other brain diseases.”