Tao Zheng - Nanoagents fight brain cancer

Nanoagents fight brain cancer

Tuesday 20 Oct 20

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Tao Zheng
PhD student
DTU Health Tech

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Yi Sun
Groupleader, Associate Professor
DTU Health Tech
+45 26 67 39 98

Chemodynamic therapy (CDT)

A type of therapy that initiates destruction of tumour cells or increases the sensitivity to other anti-tumour therapies such as chemotherapy and radiotherapy by amplifying intracellular oxidative stress.

DTU Health Tech researchers lead by Associate Professor Yi Sun have constructed a new type of nanoagent to suppress glioblastoma – a common type of tumour originating in the brain.

Glioblastoma is the most malignant cancer in our central nervous system. Annually, this type of cancer affects 3 out of 100,000 adults, and accounts for 52% of all primary brain tumours. The mainstay of treatment is surgery, followed by radiation and chemotherapy. Due to the aggressive nature and the localization in the brain, standard therapies are ineffective in managing this devastating disease.

With a 5-year survival rate of less than 10% and an average survival rate of only 15 months, glioblastoma remains a major challenge in the field of oncology. Developing new treatments for glioblastoma will be of high importance for both the patients and the healthcare system.

Crossing the tricky blood-brain barrier

The blood-brain barrier is a structure surrounding the blood vessels in the brain to protect the brain from harmful substances from the blood stream. It only allows specific molecules such as various nutrients, and macromolecules such as glucose, water and amino acids that are crucial to neural function, to pass. Development of drugs for glioblastoma treatment is very challenged by the presence of this highly restrictive blood–brain barrier.

Previous attempts to cross the blood-brain barrier with various antibodies have not been very effective. Associate Professor Yi Sun and her colleagues found that it is possible for nanoparticles to cross the blood-brain barrier without any antibodies if their size is sufficiently small and the circulation time is long.

Yi Sun explains: “Attributed to the small size (50 nm) and excellent biocompatibility, our protein nanoparticles managed to accumulate at the glioblastoma tumour site. Compared to the active targeting tried in previous studies, our passive targeting showed enhanced delivery efficiency and reduced side effect.”

A new type of nanoagent

The nanoparticles are made up of a hybrid protein nanostructure consisting of hemoglobin (Hb) and glucose oxidase (GOx) fabricated via proper assembling and crosslinking techniques.

“We injected the nanoparticles into the glioblastoma-bearing mouse models. And they crossed the blood–brain barrier and accumulated at the tumour site. In the acidic tumour microenvironment, the nanoparticles were able to efficiently produce reactive oxygen species to kill the cancer cells. For mice treated with the nanoparticles, the growth of glioblastoma tumour was significantly inhibited and the survival rate was enhanced,” Associate Professor Yi Sun says.

Another advantage of this new type of chemodynamic therapy (CDT) agent is its high biocompatibility and biodegradability as it consists entirely of natural proteins. Conventional types of CDT agents mainly utilize metal-based inorganic materials as catalysts, making neurotoxicity a major concern. The research team has shown that their protein nanoparticle could be an attractive alternative to the inorganic CDT agents to significantly improve the safety of the therapy.

The work is in collaboration with Nanjing Normal University and Nanjing Drum Tower Hospital in China, who as a next step will further investigate safety and efficiency of the nanoagent, and explore the possibilities of clinical transition towards a new treatment for glioblastoma.

Read the full paper in Nano-Micro Letters

Photo caption: PhD student Tao Zheng is checking the cytotoxic effects of the nanoagents on cancer cells

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