We have determined the affinity of the polymers for oestrogen receptor is similar compared to normal antibodies, and thus high selectivity can be guaranteed. This affinity is not impacted by incorporating the drug in the system.
Once this was established, assays were performed to show drug loading over time in two cell lines, one positive for oestrogen receptor, and one negative (another type of breast cancer cells). It was clear that the drug-loaded polymers showed temporal release of doxorubicin and were both more efficient and more selective in killing oestrogen positive breast cancer cells, as evidenced by higher cytotoxicity. Selective binding of the polymers to oestrogen receptor was also confirmed with confocal imaging. This did not just enable quantification of the results, it was also clearly shown that the polymers can enter the nucleus, which explains why the efficacy of the drug is enhanced. This is the first system that uses these specific (double imprinted) polymers for targeting a receptor that is present in the nucleus. During the secondment at UCL, the drug efficacy was also tested in 3D cell lines that are more representative of cancer growth in the human body. We have performed the experiments but are awaiting the analysis of the imaging. This will increase the novelty of the work as normally researchers do not go beyond 2D cell studies.
There have been several papers that have been written on drug delivery as part of this Marie Curie fellowship. Besides collaboration with UCL, there was also collaboration with the University of Sheffield, Guru Nanak Dev University in India and FH Krems in Austria; the Marie Curie fellow supervised an exchange student from Krems and published the results that were obtained on using alternative polymer-based systems for drug delivery. The results have been presented at several conferences and will be presented at an international conference in Las Vegas in July 2023, which is considered one of the most prestigious conferences on drug delivery in the world. The Marie Curie fellow was also able to attract an additional 10k in funding via internal sources for an ongoing collaboration with UCL.
We are now writing up the final results that include the studies in 3D models and aim to submit a manuscript this summer. The results have been presented to industrial partner MIP Discovery on several occasions and one member of MIP Discovery will be included as co-author on the upcoming publication.
