The nose-brain pathway: exploring the role of trigeminal nerves in delivering intranasally administered antidepressant

A study of trigeminal nerves reveals how the intranasal administration of the novel glucagon-like peptide-2 can produce anti-depressant effects. 

In a recent study, Japanese scientists have developed a novel concept of a nose-to-brain system for the clinical application of neuropeptides. They developed a derivative of glucagon-like peptide-2 and found that when administered intranasally, it is efficiently delivered through the trigeminal nerve to the site of action and exhibits antidepressant-like effects. This is the first demonstration in the world that intranasally administered neuropeptides reach the brain (hippocampus and hypothalamus) via neurons.

Intranasal (in.) administration has been garnering increasing popularity as a non-invasive approach to deliver drugs directly to the brain. This approach involves the respiratory or olfactory epithelia of the nasal mucosa through which the drugs reach the central nervous system (CNS). Transport from the respiratory epithelium via the trigeminal nerve is considerably slower than transport from the olfactory epithelium route via the olfactory bulb (OB) or cerebrospinal fluid (CSF). However, only a small portion of the nasal mucosa in humans is made up of olfactory epithelium, propelling researchers to focus on improving in. drug delivery time through the predominant respiratory epithelium.

To facilitate this, a team of researchers including Professor Chikamasa Yamashita from Tokyo University of Science, Japan, developed a novel drug to test its uptake efficacy by the CNS.

To offer more insight, Prof. Yamashita states: “In a previous study, we combined functional sequences (namely, a membrane permeability-promoting sequence [CPP] and an endosomal escape-promoting sequence [PAS]) to glucagon-like peptide-2 (GLP-2), which is effective against treatment-resistant depression, so that it can be efficiently taken up by neurons. Using this, we aimed to construct a nose-to-brain system mediated by the trigeminal nerve in the respiratory epithelium”.

 

Intranasal administration of PAS-CPP-GLP-2 results in its delivery to the brain via trigeminal axons of the trigeminal nerves. Source: Tokyo University of Science

 

While studying the uptake of this novel PAS-CPP-GLP-2 by the CNS, the team noted that its anti-depressant effects via in. administration remained on par with intracerebroventricular (icv.) administration at identical doses. Therefore, Prof. Yamashita and his colleagues elucidated a nose-to-brain transfer mechanism to explain why intranasally administered GLP-2 derivatives show drug effects at the same dose as intracerebroventricularly administered GLP-2 derivatives. The team’s findings have been documented in a study made available online on 30 September 2022 in Volume 351 of the Journal of Controlled Release.

The team performed icv. and in. administration of PAS-CPP-GLP-2 into mice. The amount of drug transferred to the whole brain was quantified by enzyme-linked immunosorbent assay (ELISA). Surprisingly, the ELISA revealed that a much smaller amount of intranasally administered PAS-CPP-GLP-2 reached the brain than intracerebroventricularly administered PAS-CPP-GLP-2. However, both icv. and in. administration showed efficacy at the same dose. This is attributed to the fact that icv. administration introduces drugs to the place of origin of CSF (ventricle), causing them to diffuse into the CSF and spread through the brain. Since the CSF is present in the spaces outside the capillaries of the brain, the team saw that a large portion of PAS-CPP-GLP-2 was likely to stay here without being transported to its working sites of action. On the other hand, nasally administered GLP-2 derivatives were rapidly taken up by the trigeminal nerve of the respiratory epithelium, and efficiently reached the site of action while transiting neurons.

Prof. Yamashita explains: “This suggests that the peptide delivered to the site of action by icv. administration is present in large amounts in the brain but only in very small amounts, as it remains in the perivascular space. On the other hand, intranasally administered PAS-CPP-GLP-2, unlike icv. administration, may be transferred to the site of action without passing through the CSF or perivascular space”.

These results prompted the team to identify the central transfer drug delivery route following in. administration. This route involved the principal sensory trigeminal nucleus, followed by the trigeminal lemniscus of the trigeminal nerve, and led to the drug’s working sites. Finally, it was discovered that the migration of PAS-CPP-GLP-2 via nerve transit was the reason behind its pharmacological activity despite its low levels in the brain upon in. administration.

Prof. Yamashita explains, “This is the world’s first drug delivery system that allows intranasally administered peptides to be delivered to the central nervous system via nerve cells, delivering peptides to the site of action with the same efficiency as icv. administration.”

Speaking about the future applications of the team’s findings, Prof. Yamashita concludes: “Current data suggests the possibility of extending the use of this system from treating depression to delivering drugs in patients with Alzheimer’s disease. It is therefore expected to be applied to neurodegenerative diseases with high, unmet medical demand.”

Reference:

DOI: https://doi.org/10.1016/j.jconrel.2022.09.047

Title of original paper: Involvement of trigeminal axons in nose-to-brain delivery of glucagon-like peptide-2 derivative

Journal: Journal of Controlled Release

Lingnan University to help train the public administrators of the future

Across the globe, the challenges faced by those charged with the implementation of public policy are growing all the time. Governments at local, regional and national levels are having to address issues ranging from poverty and unemployment, to disease and environmental degradation, while, at the same time, ensuring their approach is inclusive and, as far as possible, transparent.

In response to these challenges, the New Public Management movement – characterised by its emphasis on concepts such as flat hierarchies, customer orientation, contracting out and market-based governance – has been widely embraced. The new generation of ICTs—big data and AI—have been applied to automatic decision-making within the public services, a development which has far-reaching effects on public administration reform.

To help meet the resulting demand for graduates with the skills required to ensure coordinated, effective and accountable administration, Lingnan University will launch its new Master of Social Sciences in Comparative Public Administration (MSocScCPA) programme in September 2023.

Lingnan’s new programme

Students on the one year full-time or two year part-time MSocScCPA programme will analyse development, public policy and governance issues, from comparative and international perspectives. They will also have the opportunity to attend international symposium and conferences, conduct research projects and attend field trips and seminars.

The programme culminates in the Comparative Public Administration Capstone Project and Symposium Presentation course, which will enable students to apply what they’ve learned to the analysis of real-world public policy and developmental issues.

The MSocScCPA builds upon the Master of Cities and Governance, Master of China and Regional Studies, and the Doctor of Policy Studies programmes, which have been successfully launched by Lingnan’s School of Graduate Studies and Institute of Policy Studies.

Since Lingnan has forged a network of international and national collaborative partnerships, programme participants will hear from a range of renowned speakers from across the globe, and connect with a number of policy studies institutes within the region.

Opportunities for programme graduates in the GBA

One of Lingnan’s key development strategies is to strengthen the university’s connection with China’s Greater Bay Area (GBA), a world-class, city cluster comprising Hong Kong, Macau, and nine other cities in Guangdong Province. Despite the region’s vast potential, the varying levels of economic and social development across the GBA pose challenges for cross-regional public administration in fields such as environmental governance, social mobility, and global risk resilience. In addition, the need to adopt a more humane approach to public administration, and pay greater attention to the grievances of the citizenry, has also become more pressing. Resolving these difficulties, and meeting such needs, will require an end to the opaqueness and the secrecy which has formerly surrounded government activities, and the embracing of accountability and transparency, instead.

Within the GBA, MSocScCPA graduates will be well equipped to meet the rapidly growing demand in both the public and private sectors – in government departments, and in bodies such as NGOs, consultancies and think tanks – where they can work to promote speedy development along with good governance.

Please click here for details of MSocScCPA.

Trial by wind: testing the heat resistance of carbon fiber-reinforced ultra-high-temperature ceramic matrix composites

Researchers use an arc-wind tunnel to test the heat resistance of carbon fiber-reinforced ultra-high-temperature ceramic matrix composites. 

Carbon fiber-reinforced ultra-high-temperature ceramic (UHTC) matrix composites are extensively used in space shuttles and high-speed vehicles. However, these composites suffer from a lack of oxidation resistance. Recently, researchers from Japan tested the heat resistance of these composites at very high temperatures, providing insight into the modifications needed to prevent UHTC degradation. Their findings could have huge implications for the manufacture of space shuttle orbiters.

Carbon fiber-reinforced carbon (C/C) is a composite material made of carbon fiber reinforced in a matrix of glassy carbon or graphite. It is best known as the material used in hypersonic vehicles and space shuttle orbiters, which cruise at speeds greater than Mach 5. Since the 1970s, it has also been used in the brake system in Formula One racing cars. Even though C/C has excellent mechanical properties at high temperatures and inert atmospheres, it lacks oxidation resistance in these conditions, making its widespread use limited.

Researchers have found that ultra-high-temperature ceramics (UHTCs), which include transition metal carbides and diborides, show good oxidation resistance. In previous studies, zirconium-titanium (Zr-Ti) alloy infiltration has shown promising results for improving the heat resistance of carbon fiber-reinforced UHTC matrix composites (C/UHTCMCs). However, their use at high temperatures (>2000 °C) is not known.

Set against this backdrop, a group of researchers from Japan have evaluated the potential utility of Zr-Ti alloy-infiltrated C/UHTCMCs at temperatures above 2000 °C. Their study, led by Junior Associate Professor Ryo Inoue from Tokyo University of Science (TUS), was published in the Journal of Materials Science and made available online on October 27, 2022. The research team consisted of Mr. Noriatsu Koide and Assistant Professor Yutaro Arai from TUS, Professor Makoto Hasegawa from Yokohama National University, and Dr. Toshiyuki Nishimura from the National Institute for Materials Science.

Speaking of the motivation behind their study, “The research is an extension of the research and development of ceramics and ceramics-based composite materials. In recent years, we have received inquiries from several manufacturers of heavy industries regarding materials that can be used at temperatures above 2000 °C. We have also started to work with these manufacturers to develop new materials,” says Prof. Inoue.

The C/UHTCMC was manufactured using melt infiltration, which is the most cost-effective way to fabricate these materials. To study the applicability of this material, three types of C/UHTCMCs were fabricated with three different alloy compositions. The three alloy compositions used had varying atomic ratios of Zr:Ti. To characterize the heat resistance, the team used a method called arc-wind tunnel testing. This method involves exposing the material to extremely high enthalpy airflow inside a tunnel, similar to conditions that spacecrafts experience while re-entering the atmosphere.

The team found that the amount of Zr in the alloy had a strong effect on the degradation of the composite for all temperatures. This is owing to the thermodynamic preference for the oxidation of Zr-rich carbides compared to Ti-rich carbides. Further, the Zr and Ti oxides formed on the composite surface prevented further oxidation, and the oxide composition depended on the composition of the infiltrated alloys. Thermodynamic analysis revealed that the oxides formed on the composite surface were composed of ZrO2, ZrTiO4, and TiO2 solid solutions.

At temperatures above 2000 °C, the thickness and weight of the samples increased with the Zr content of the composites after the arc-wind tunnel tests. The team also observed that the melting point of the surface oxides increased as the Zr content increased. For temperatures above 2600 °C, the only oxides formed were liquid-phase, requiring a thermodynamic design of the matrix composition to prevent the recession of UHTC composites.

“We have successfully studied the degradation of C/UHTCMC at temperatures above 2000 °C using thermodynamic analysis. We have also shown that the matrix design needs modification to prevent the degradation of the composites. Our research has the potential to contribute to the realization of ultra-high-speed passenger aircraft, re-entry vehicle, and other hypersonic vehicles,” concludes Prof. Inoue.

These results could have important consequences in the production of advanced space shuttle orbiters and high-speed vehicles.

Reference:

DOI: https://doi.org/10.1007/s10853-022-07861-x

Title of original paper: Degradation of carbon fiber-reinforced ultra-high-temperature ceramic matrix composites at extremely high temperature using arc-wind tunnel tests

Journal: Journal of Materials Science

Ukraine’s National Technical University holds annual international scientific conference

The annual international scientific conference MicroCAD-2022 was held at the National Technical University “Kharkiv Polytechnic Institute” (NTU “KhPI”) in October this year. And although the conditions were extremely difficult, which was caused by a terrible war with missile attacks, including during the plenary session, this online conference became a top-level event.

Great honour was given to MicroCAD-2022 by the Nobel Prize Laureate in Physics and the Oliver Buckley Award winner, Professor at Princeton University, member of the Royal Scientific Society (Great Britain), and expert in the theory of condensed media Frederick Duncan Michael Haldane, who spoke at the plenary session. The scientist congratulated the participants of the Conference and noted that the science continues to develop in Ukraine in spite of such hard times. Professor Haldane’s speech was devoted to the physical foundations of creating a quantum computer –  “The hope for a topologically-protected quantum computer”: https://www.youtube.com/watch?v=j1BrgENaP6o.

Rector of NTU “KhPI”, Corresponding Member of the National Academy of Sciences of Ukraine, and Laureate of the State Prize in the Field of Science and Technology, Professor Yevgen Sokol, made a report “Education and Science as the Basis for Innovative Development of the state” at the plenary session. He stressed the important role of the Kharkiv Polytechnic, the contribution of its students, teachers, and scientists to the development of innovative products and approaches to education.

Chairman of the Supervisory Board of NTU “KhPI” partner, one of Kharkiv’s leading industrial enterprises – i.e. PJSC “TURBOGAS”, Oleg Kuprigin spoke about the combination of advanced scientific achievements and production technologies in cooperation with Kharkiv Polytechnics.

In addition, reports were made by the founder of the scientific direction “Electrochemical Design, Diagnostics and Prediction of the Properties of Functional Coatings”, Laureate of the National Prize of Ukraine named after Boris Paton, Head of the Physical Chemistry Department of NTU “KhPI”, Doctor of Technical Sciences, Professor Mykola Sakhnenko.

As a result, the participants of the International Scientific Conference MicroCAD-2022, and first of all the plenary session, received strong support for their scientific activities, recognition of the importance of science and education in economic recovery, and innovative development of Ukraine.

An eye-opening summer program: linguistic journey at FBM, UiTM

The Faculty of Business and Management (FBM), Universiti Teknologi MARA (UiTM), Malaysia, Puncak Alam Campus, hosted a summer program for 11 non-business students from the National Institute of Technology, Ube College (NITUC), Japan. The main objective of the summer program was for the students to embark on a linguistic journey to acquire English while learning the fundamentals of business. To attend to this, customised business modules were created for this group of students.  Several senior faculty members of FBM participated as facilitators and speakers for this one-month summer program, which ran from August 25th to September 24th of 2022. They shared their business experience, expertise and knowledge with the students.

The NITUC students found this summer program to be eye-opening as it enriched their business knowledge and experience while improving their English skills. The program offers a variety of activities with several buddy sessions and provide opportunities for cultural immersion. In addition to learning about business matters, the program added more colour into the students’ lives as it allowed them to experiment with different learning styles, foster connections with their peers, facilitators, and lecturers from Malaysia as well as discover Malaysian history, cultures and traditions. As students were encouraged to talk, ask questions, and contribute throughout the program, it boosted the students’ English proficiency.

Yamashita Kao, 16, a student from the Department of Chemistry and Materials Technology, said that the program was “a good experience for me because I learned a lot about Malaysian traditions and was able to communicate in English with the buddies and teachers in a fun and easy way.  I look forward to meet everyone again in the future”. Similarly, Sasamoto Keita, 17, a student from the Department of Electrical and Electronic Engineering stated that “the summer program is fun and exciting. I wish to visit Malaysia again”.

Kamimura Tsukino, 18, from the Department of Control and Information Engineering explained the summer program was “exciting since I can communicate in English with my buddies and teachers. They were all very kind”.

Not only did the students give the program great reviews, NITUC’s Sensei, Ms. Siti Aisyah Mokhtar concurred.  She said, “During this program, the students gained so much knowledge and experience that they could not have learned anywhere else.  They enjoyed their time at UiTM and found that after a month, they could communicate more effectively in English. Their improvement has impressed us.”

With the enormous success and accomplishment of this 2022’s summer program, NITUC, Japan eagerly anticipating the Linguistic Journey @ FBM, UiTM 2.0, which is set to begin in September 2023. For both FBM, UiTM and NITUC, Japan, they are committed to making the summer program a yearly event. This summer program is part of FBM’s international mobility drive in supporting UiTM’s aspiration to become a globally renowned university (GRU) in 2025.

For the program’s video, go to https://www.youtube.com/watch?v=v3yxT96p1zw.

Vitamin D deficiency leads to dementia

Dementia is one of the major causes of disability and dependency among older people worldwide, affecting thinking and behaviours as you age. But what if you could stop this degenerative disease in its tracks?

A world-first study from the University of South Australia could make this a reality as new genetic research shows a direct link between dementia and a lack of vitamin D.

Investigating the association between vitamin D, neuroimaging features, and the risk of dementia and stroke, the study found:

  • low levels of vitamin D were associated with lower brain volumes and an increased risk of dementia and stroke,
  • genetic analyses supported a causal effect of vitamin D deficiency and dementia,
  • in some populations as much as 17 per cent of dementia cases might be prevented by increasing everyone to normal levels of vitamin D (50 nmol/L).

Dementia is a chronic or progressive syndrome that leads to deterioration in cognitive function. About 487,500 Australians live with dementia and it is the country’s second leading cause of death. Globally, more than 55 million people have dementia with 10 million new cases diagnosed every year.

Supported by the National Health and Medical Research Council, the genetic study analysed data from 294,514 participants from the UK Biobank, examining the impact of low levels of vitamin D (25 nmol/L) and the risk of dementia and stroke. Nonlinear Mendelian randomisation (MR) – a method of using measured variation in genes to examine the causal effect of a modifiable exposure on disease – were used to test for underlying causality for neuroimaging outcomes, dementia, and stroke.

Senior investigator and Director of UniSA’s Australian Centre for Precision Health, Professor Elina Hyppönen, says the findings are important for the prevention of dementia and appreciating the need to abolish vitamin D deficiency.

“Vitamin D is a hormone precursor that is increasingly recognised for widespread effects, including on brain health, but until now it has been very difficult to examine what would happen if we were able to prevent vitamin D deficiency,” Prof Hyppönen says.

“Our study is the first to examine the effect of very low levels of vitamin D on the risks of dementia and stroke, using robust genetic analyses among a large population.

“In some contexts, where vitamin D deficiency is relatively common, our findings have important implications for dementia risks. Indeed, in this UK population, we observed that up to 17 per cent of dementia cases might have been avoided by boosting vitamin D levels to be within a normal range.”

The findings are incredibly significant given the high prevalence of dementia around the world.
“Dementia is a progressive and debilitating disease that can devastate individuals and families alike,” Prof Hyppönen says.

“If we’re able to change this reality through ensuring that none of us is severely vitamin D deficient, it would also have further benefits and we could change the health and wellbeing of thousands.”

HKBU Global University Film Awards 2022 presents gold award to France’s Le Fresnoy

Organised by the Academy of Film (AF) at Hong Kong Baptist University (HKBU), the Global University Film Awards (GUFA) 2022 held its magnificent award presentation ceremony in virtual mode on 11 November. The entry from France’s Le Fresnoy clinched the Gold Award. (The full list of winners is attached in the appendix at the end of this article).

This year’s award presentation ceremony was broadcast live online in a wonderfully designed cinematic setting, using virtual sets and advanced technology to recreate classic scenes in blockbusters such as The Matrix, the Harry Potter film series, and In the Mood for Love. In his opening remarks at the ceremony, Dr Clement Chen, Chairman of the Council and the Court of HKBU, shared the delights of seeing GUFA held for the third time. “We hope to stand as a beacon of encouragement to emerging filmmakers, allowing them to create their art without commercial considerations and industry pressures. At university, they are free to let their imagination fly, share their concerns and explore creative ideas. We at HKBU embrace these ideals and, for over four decades, have been offering the finest teaching and training in the cinematic arts. We continue to celebrate this legacy today as we nurture tomorrow’s filmmakers.”

In his speech, Professor Alexander Wai, President and Vice-Chancellor of HKBU, said: “HKBU is the first institution in Hong Kong to offer film and video production programmes and we always have our eyes on the future. Filmmaking is a global community, and GUFA is a way for all of us to celebrate new young talents from all over the world. It gives me great delight to have a sneak peek at the future voices of filmmaking and to celebrate their progress.”

Widely known as the “University Oscars”, this year GUFA received more than 2,300 submissions from about 100 countries and regions. Celebrated professionals in the film industry, including directors Ms Mabel Cheung, Mr Derek Tsang, Ms Jessey Tsang, Mr Ray Yeung, and actress/producer Ms Josie Ho presented 15 awards to young film talents from all over the world, letting them shine on a glamorous virtual stage.

To further showcase the exemplary works at GUFA 2022, a public screening of the winners was held on 15 November at HKBU. Members of the public were welcome to attend. For more information, please refer to the GUFA website, GUFA Facebook page and GUFA YouTube channel.

GUFA recognises the excellence of film productions by university students from across the world by connecting the global film community and its audiences with outstanding work and groundbreaking ideas presented by the participants. The event not only showcases the students’ talents but also fosters the exchange of ideas and enhances professional networks, building synergy between young regional talents and the international creative industry.

Appendix: Award winners

Award

Winning film

University

Best Narrative

Good German Work

Konrad Wolf Film University of Babelsberg, Germany

Special Mention of Narrative

When Summer Ends

Hong Kong Baptist University, Hong Kong

Best Cine-VFX

Little Gestures

Pearson College London, United Kingdom

Special Mention of Cine-VFX

17 Souls

University of Television and Film Munich (HFF München), Germany

Best Documentary

Pupus

Centro Sperimentale di Cinematografia- Sede Sicilia, Italy

Special Mention of Documentary

Broken

Yangon Film School, Myanmar

Best Experimental Film

$75 000

Le Fresnoy, France

Special Mention of Experimental Film

In Plain Sight

Chulalongkorn University, Thailand

Best Animation

Graziano and the Giraffe

Centro Sperimentale di Cinematografia, Italy

Special Mention of Animation

A Dog under Bridge

China Academy of Art, Mainland China

Best Director

To Each Your Sarah

Korea National University of Arts, South Korea

Best Script

Russian Vodka

University of Applied Science and Technology, Iran

Gold Award

$75 000

Le Fresnoy, France

HKBU Academy of Film’s Choice

Intimate Distance

Hong Kong Baptist University, Hong Kong

HKBU Academy of Film’s Choice Special Mention

Love Delivery

Hong Kong Metropolitan University, Hong Kong

Universitas Airlangga hosts 2022 WUACD Summit and Conference

The World University Association for Community Development (WUACD) proves that an institution could contribute significantly to the community. In 2018, Universitas Airlangga (UNAIR) initiated WUACD for more impactful community development programs. The platform is an integrated collaboration of universities worldwide for developing communities to support Sustainable Development Goals (SDGs).

This year, UNAIR hosted the WUACD Summit and Conference in Surabaya. The first day of the Summit was held on Wednesday, November 9, 2022, at the Management Building of UNAIR, Surabaya. The summit discussed several topics, including WUACD continuity and its programs.

UNAIR presented some of its ongoing and completed programs on community development, such as the Ksatria Airlangga Floating Hospital (RSTKA) and Psikologi Mencari Bakat (Psychology Got Talent).

Prof. Dr. Ni Nyoman Tri Puspaningsih MSi, the Vice-Rector for Research, Innovation, and Community Development, explained the contributions of RSTKA to community development service. “The floating hospital was established to reach numerous remote areas in Indonesia. The RSTKA helps distribute main necessities, such as energy, food, or health, especially for the COVID-19 vaccination program,” Prof. Nyoman said. The archipelagic conditions of Indonesia make equal health service distribution challenging to achieve. “Apart from the health services, RSTKA also provides education for the community,” she continued.

Dr Niko Azhari Hidayat Sp BTKV(K), the coordinator of WUACD health and environment program, explained the Psikologi Mencari Bakat (PMB). The program was managed by UNAIR Faculty of Psychology (FPsi) in collaboration with psychology practitioners and intended for children with disabilities. Since 2021, PMB has collaborated with WUACD to invite international guest judges from Malaysia. At that time, PMB gave 466 children with disabilities the opportunity to show their talents and interests. “The program distinctively stands out as it boosts children’s confidence. They can play, sharpen their skills, and gain potential abilities from the surroundings,” he ended.

The summit also held a signing session of memorandums of understanding between the participating transnational institutions.

HKBU develops multifunctional nanoparticle for diagnosis and treatment of glioma

A Hong Kong Baptist University (HKBU) collaborative research team has synthesised a nanoparticle named TRZD that can perform the dual function of diagnosing and treating glioma in the brain. It emits 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 nanoparticle offers hope for the early diagnosis and treatment of glioma, especially cerebellar glioma, which is even harder to detect and cure with existing methods.

The research results have been published in Science Advances, an international scientific journal.

Limitations of existing diagnostic and therapeutic approaches

Glioma is the most common form of malignant primary brain tumour, and it accounts for about one-third of all brain tumours. Magnetic resonance imaging (MRI) is commonly used to diagnose glioma, but the technology is not that sensitive. Cerebellar glioma, a relatively rare brain tumour, is even harder to detect with MRI. To facilitate early detection and treatment, an alternative method with improved sensitivity and precision is needed to diagnose glioma.

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. To enhance doxorubicin’s clinical efficacy and minimise its side effects, a novel approach is needed to apply the drug to tumour cells in a more targeted manner.

In response to the diagnostic and therapeutic needs of glioma, 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 has the characteristic of emitting NIR persistent luminescence after excitation with ultraviolet (UV) light. The basic structure of TRZD is a combination of nanoparticles, loaded with the mesoporous structure of silica, which makes it 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. T7 peptides have a strong affinity for transferrin receptors which are abundant on the surface of tumour cells, and they can facilitate TRZD’s penetration through the blood-brain barrier.

An imaging probe for glioma diagnosis

The research team evaluated the efficacy of TRZ (i.e. TRZD without doxorubicin) in diagnostic imaging for glioma with a mouse model. TRZ particles were first excited by UV light to initiate luminescence. Mice with tumour tissues injected into their cerebrum and cerebellum were then treated with TRZ. In the following 24 hours, TRZ luminescence was detected at the tumour sites of the mice.

However, when the same experiment was conducted with TRZ without T7 peptides, and TRZ without both the red blood cell membrane coating and T7 peptides, no luminescence was detected at the tumour sites of the mice. The results show that the red blood cell membrane coating can prolong the function of TRZ by stabilising the nanoparticle, and it can slow down its natural uptake by the human body. On the other hand, T7 peptides are instrumental in TRZ’s penetration into and accumulation in tumour cells, so that it can perform its imaging function for glioma.

Dr Wang said: “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.” 

TRZD inhibits the growth of glioma and extends the lifespan of mice

The research team further evaluated the anti-tumour efficacy of TRZD using a group of mice who had had their cerebrum and cerebellum injected with tumour tissues. After applying TRZD for 15 days, the average diameter of their tumours was reduced to 1 mm. They 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 said: “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.”

EdUHK shares knowledge across Asia

Four Doctor of Education students from Cambodia recently arrived at The Education University of Hong Kong (EdUHK) as part of a World Bank project.

The students were awarded doctoral scholarships funded through the World Bank’s Higher Education Improvement Project. The project aims to improve the quality of higher education learning and teaching, as well as to enhance the research capacity and governance of the Cambodian higher education sector. To attain these goals, EdUHK is collaborating with RUPP, and has been working in partnership with the south-east Asian country’s ministry of education and six universities to set up the Centre of Excellence in Higher Education Teaching and Learning Innovations (CEHETLI).

Passing the torch

With the support of the EdUHK-CEHETLI team, the students will continue their learning journey at the University to build their capacity for quality research, teaching and learning. After graduation, they will serve as key personnel to manage the Centre and its activities, and contribute to quality enhancement of higher education teaching and learning in Cambodia. Also part of the World Bank project, EdUHK and CEHETLI have co-organised a series of policy dialogue events. The fourth of these took place online in February and brought together 48 university leaders and senior higher education management officials from Cambodia and EdUHK, to celebrate the 21 master teachers’ successful completion of the Graduate Certificate in Teaching and Learning in Higher Education programme. This provides a variety of learning opportunities for the master teachers to build their capacity for quality higher education teaching and learning.