Development and characterisation of a peptide: bisphosphonate nanoparticle for the treatment of breast cancer

Here we report highly stable NPs formed with Risedronate (R-RIS NPs), that portrayed superior direct anti-tumour effects in vitro and in vivo in BC models, compared to RIS administered alone. Molecular studies showed R-RIS NPs were on target within the cell, inhibiting the main mechanism of action of N-BPs, known as the mevalonate pathway. Anti-tumour effects were confirmed with subsequent increased cytotoxicity and apoptotic cell death following R-RIS NP treatment, and inhibition of the AKT cell survival pathway compared to untreated and RIS alone.

Furthermore, utilizing two in vivo models (MDA-MB-231 and 4T1), R-RIS NP treatment significantly reduced tumour growth, prolonged survival, increased tumour doubling times and prevented visceral metastasis of the primary tumour to the lungs. Biodistribution studies showed significantly more drug accumulation in the tumour with RALA delivery, and significantly higher accumulation still evident three weeks post administration.This thesis has demonstrated the characterisation of a novel therapeutic strategy in-cooperating the FDA-approved N-BP Risedronate into the RALA delivery system.

R-RIS NPs presents great potential to improve treatment for early-stage BC (ESBC) by inhibiting primary tumour growth and preventing distant metastasis.<br><br><br><i>Thesis embargoed until 31 July 2027 </i><br>