Targeted drug delivery to treat brain tumours in children

US researchers have developed a drug delivery approach that uses nanoparticles to enable more effective and targeted delivery of anticancer drugs to treat brain tumours in children. Described in the journal Nature Materials, the technology allows for the enhanced delivery of anticancer drugs to the specific locations of brain tumours while sparing normal brain regions, resulting in improved effectiveness and reduced toxicities of anticancer drugs.

Medulloblastoma is the most common malignant paediatric brain tumour, accounting for about 20% of all brain tumours in children and considered incurable in nearly 30% of patients. Even children who are ‘cured’ experience severe long-term disabilities and health issues, primarily due to the adverse side effects of radiation and chemotherapy. Furthermore, site-directed drug delivery to the affected brain tissue is hindered by the blood–brain barrier.

The researchers made use of a normal mechanism that the immune system uses to traffic white blood cells to sites of infection, inflammation or tissue injury. Rather than randomly sending immune cells throughout the body, there is a homing mechanism on activated blood vessels that immune cells use to go where they are needed. The researchers used this homing feature, which is also found within brain tumour blood vessels, to target their drug-loaded nanoparticles to the site of the disease and not the normal brain regions.

“Certain proteins appear on blood vessels at sites of inflammation that help white blood cells exit the bloodstream. They work like police officers at the site of a car accident, who let in emergency personnel to help,” said senior author Dr Daniel Heller, from the Memorial Sloan Kettering Cancer Center. “We sent in our own emergency personnel, in the form of drug-loaded nanoparticles, composed of certain sugar molecules that can target these same proteins.”

Using their drug delivery platform in a mouse model of medulloblastoma, the research team was able to enhance the efficacy of an anticancer drug that could potentially be useful for a subset of medulloblastoma patients, but which is currently limited by the bone toxicity it secondarily creates in children.

“We show that we can more successfully deliver lower doses of the drug in a more effective manner to the specific sites of tumour within the brain, while sparing the bone toxicity that is seen in younger patients,” said co-senior author Dr Praveen Raju, from the Mount Sinai Health System.

“In addition, we showed that this targeted drug delivery approach is further enhanced with very-low-dose radiation, which is a standard therapy already used for most children and adults with primary and metastatic brain tumours.”

The researchers said the continued development of their method to improve the transport of materials across the blood–brain barrier and other sites will help to increase the efficacy of several classes of approved and experimental therapeutics, to treat cancers in the brain and other sites as well as other inflammation-related diseases.

“Our blood–brain barrier drug delivery approach has the potential to improve the delivery of drugs for other paediatric brain tumours and localised diseases in the brain in both children and adults, including focal epilepsy, multiple sclerosis, stroke and possibly neurodegenerative disorders,” Raju said.

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