Introduction Bisphosphonates (BPs) are commonly used for the treatment of osteoporosis, but recent evidence indicates an anti-cancer potential through the inhibition of the melovanate pathway. However, this therapeutic potential of BPs has been hindered by poor bioavailability and toxicity in addition to gastrointestinal adverse effects. This study utilises an amphipathic peptide termed RALA to condense BPs into nanoparticles to deliver a greater therapeutic effect thereby enhancing bioavailability1,2. Experimental. The size and zeta potential of RALA/BP complexes at a range of w/w ratios were measured using a Malvern Zetasizer over a range of time points and temperatures. Cellular uptake following treatment of LN-229 glioblastoma cells with RALA/BP was analysed using flow cytometry and cell viability assessed using MTS reagent. 3-D LN-229, T98G and PC-3 spheroid models were treated with free BP and RALA/BP nanoparticles (NPs) to observe growth delay over a 10-day period. Results. RALA successfully complexed BPs such as alendronate and risedronate, to produce stable cationic NPs <100 nm from 4-40oC over a 28-day period. Results also indicated successful complexation of RALA with an Alexa-Fluor 647 tagged risedronate (AF647-RIS) to produce NPs of an optimal size for cellular uptake by LN229 glioma cells. AF647 was detectable in LN229 cells following 30 min treatment with RALA/AF647-RIS NPs with 94% positive uptake vs AF647-RIS alone (36.7% uptake). Dose-response studies induced a significant potentiation factor in vitro and reduced tumour growth in vivo. It was observed that the RALA/BP nanoparticles were more effective anticancer agents than free BP.
|Publication status||Published - 20 Sep 2018|
|Event||International Conference On Nanomedicine And Nanobiotechnology – ICONAN 2018. - Europe, Rome, Italy|
Duration: 26 Sep 2018 → 28 Sep 2018
|Conference||International Conference On Nanomedicine And Nanobiotechnology – ICONAN 2018.|
|Period||26/09/2018 → 28/09/2018|
Jena, L., Singh, T. R. R., & McCarthy, H. (2018). A RALA-based nanocarrier for the intracellular delivery of bisphosphonates as anti-cancer therapeutics. Poster session presented at International Conference On Nanomedicine And Nanobiotechnology – ICONAN 2018., Rome, Italy.