Nanoparticle couriers for GBM treatments

Fast facts

• Official title: Nanoparticle delivery of microRNA in a preclinical model of glioblastoma
• Lead researcher: Professor Sebastian Brandner
• Where: University College London
• When: September 2020 – August 2022
• Cost: £114,169 over two years
• Research type: Adult, High Grade, Academic
• Award type: Expanding theories

---

What is it?

This grant will enable the researchers to investigate whether they can use tiny nanoparticles to deliver tiny pieces of key RNA into tumour cells, stopping their growth.

The nanoparticles they are developing are called polymersomes. They are like tiny biological couriers that can cross the blood brain barrier and, importantly, enter cells. This state-of-the-art technology could be the answer we’ve been looking for to conquer the blood brain barrier and deliver treatments to tumour cells.

The team, led by Professor Sebastian Brandner at University College London, will be loading the polymersomes with tiny fragments of RNA, called micro RNA (miRNA). Like DNA, RNA is a code that tells cells what to do. Using miRNA to block the larger RNA is like throwing a spanner in the cogs of a big machine. If we can find the right spanner we hope to stop the tumour-causing ‘machinery’ in its tracks.

Exciting preliminary research from this group has identified two miRNAs, called miR449a and miR183, which have promise in stopping glioblastoma (GBM), the most common high grade brain tumour in adults. These will be loaded into the polymersomes and assessed using their sophisticated model of GBM. The researchers will test different aspects of the nanoparticles, including shape, size and composition, to define the best one/s to delay tumour growth in the lab.

As part of this grant they will also expand their model by inserting a gene that ‘lights up’ the tumour cells. This will mean the tumours can be seen more clearly, and their responses to the nanoparticle treatments can be monitored over time.

This research builds upon a previously developed model system in which we have successfully reduced tumour growth with inhibitors. This project is specifically designed to build a bridge between bench and bedside.

Professor Sebastian Brandner

Why is it important?

This grant is addressing two of the most difficult challenges in brain tumour research: developing effective treatments and delivering them to the tumour. By using cutting-edge techniques in combination with the best laboratory models, we hope their work will be the foundation for new clinical trials, new treatments and ultimately a cure that defeats brain tumours.

Who will it help?

This early stage research into miR449a and miR183 has the most direct potential to help people with a glioblastoma. However the nanoparticle research has even greater prospects, and could be used to deliver treatments to any type of brain tumour.

Milestones

The team have developed a method of administering the polymersomes that is more effective than the method previously used. Additionally, it’s more easily repeated for additional doses and doesn’t appear to have any harmful side effects on its own.

Researchers have also shown that a general chemotherapy drug carried within the polymersomes can slow tumour growth and extend survival in experimental models.

Ongoing work is combining the polymersomes and the micro-RNAs in the most effective way. The team have obtained the micro-RNAs needed and have started to incorporate them into the polymersomes at different concentrations, using different methods. The next step will be to test these in their pre-clinical brain tumour models.