Scientists use tumour tissue from cancer patients to enhance testing of nanomedicines

In an important advance for the field of nanomedicine and the treatment of cancer, a team of scientists led from the Monash Institute of Pharmaceutical Sciences (MIPS) have used tumour tissue from cancer patients to better discriminate between potential nanomedicines.

Nanomedicine is a branch of medicine that harnesses nanotechnology to prevent and treat disease, with a strong focus on cancer therapeutics.

Despite an abundance of evidence to show that nanomedicine can successfully eradicate cancer tumours in preclinical research, only limited nanoformulations make it to the clinic - one of the reasons behind this failure in clinical translation has been the gap between animal and human studies.

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By utilising tumour samples directly resected from prostate cancer patients, the team of researchers have been able to compare patient samples to conventional tumours in mice in order to collect new information on the biological barriers that nanomedicines face in the clinic.

The study highlighted key differences between the two tumours, including the way the cell types forming the tumour behave, are structured and how they interact with each other.

Lead author, Dr Anna Cifuentes Rius, from MIPS said: “With prostate cancer, the ability to silence the androgen receptor plays a critical role in stopping the cancer from progressing. We know nanoparticles containing small interfering RNA (siRNA) can silence this receptor but there’s something in the human tumour environment that impedes their full potential. With access to tumour tissue from prostate cancer patients we’ve, for the first time, tested the efficacy of nanomedicines in these patient-derived explants, and compared it with 3D in vitro cell models. By using this model, we have exposed nanomedicines to what might be a more accurate scenario compared to that in a clinical setting.

“More specifically, we tested two types of nanomedicines: a commercially available lipid-based nanoparticle and our engineered porous silicon nanoparticles. Our results show that while both types of nanomedicines were able to silence the androgen receptor in the 3D in vitro cell model, only porous silicon nanoparticles silenced it in patient derived explants. This suggests that optimised design of nanomedicines using this model could facilitate their access to the target sites within the tumour environment.”

Nanoparticle-mediated delivery of therapeutics have seen explosive growth due to promising preclinical results in eradicating solid tumours and prolonging survival rates, but the link to clinical translation remains elusive.

“This model may provide a key missing piece in the pipeline towards developing successful nanomedicines,” says Dr Cifuentes Rius.

“We envision that the model will help drug delivery scientists with an interest in oncology to better formulate more efficacious nanomedicines and to help accelerate nanomedicines into the clinic by improving our understanding of the nano-tumour interface.”

The next step for the team is to consolidate this model into routine testing of nanomedicines and expand it to other cancers such as breast cancer. The goal is to use these models to understand the biology of the human clinical tumours to design and engineer better, more personalised nanomedicines.

This work was possible thanks to the established collaboration with the prostate cancer researcher, Professor Lisa Butler from the South Australian Health and Medical Research Institute and support from the Prostate Cancer Foundation of Australia.

The study has been published in the journal Advanced Healthcare Materials – the full version can be found here: https://onlinelibrary.wiley.com/doi/10.1002/adhm.202001594.