Researchers at Queen’s university Belfast have developed nanoparticles which increase (30%) the sensitivity of prostate cancer cells to radiotherapy.
Prostate cancer is one of the most common cancer diagnosed worldwide. Similar to other cancers, radiotherapy (RT) is the standard of care option for treating such localized cancers. However, a significant number of patients (20-40%) do not respond to the treatment resulting in disease progression. In addition, RT results in off target affects such as damage to neighboring healthy tissue. Therefore, it is vital to develop radiosensitizers which can substantially elevate the efficiency of RT along with limiting off-target radiation damage. Bennie et al have addressed these issues with RT efficiency in their recent study published in Nanobiotechnology.
Gold nanoparticles (AuNP) are efficient radiosensitizers, however they come up with limitations such as short systemic circulation times and poor target cell uptake. These limitations can be overcome by using cell penetrating peptides (CPP) which possess cationic, basic and fusogenic properties, and can be manipulated for intra-cellular delivery. The researchers have investigated the potential of a short synthetic CPP peptide-RALA for increasing uptake efficiency of gold nanoparticles (AuNP) and subsequent impact on radiosensitivity. These CPP possess cationic, basic and fusogenic properties RALA increased the uptake of gold nanoparticles by three folds in PC-3 and DU145 prostate cancer cell-based model systems, without any significant toxicity. RALA and AuNP are able to successfully form nano-complexes at 20:1 ratio (20ug RALA:1ug AuNP), and all formulations significantly increased the radiosensitivity of prostate cancer. The effect was highest when RALA-AuNP formulation was used at 25:1 ratio which significantly increased prostate cancer cells radiosensitivity producing dose enhancement effects (DEF) of 1.54 in PC3 cells.
This is a first study demonstrating the use of ultra-low microgram concentrations of gold nanoparticles causing radio-sensitivity enhancement in prostate cancer cells. These effects were achieved using a short peptide (RALA) to gold nanoparticles. These findings also support previous imaging study by the same team indicating RALA-AuNP nuclear accumulation.
Bennie, L.A., Feng, J., Emmerson, C. et al. Formulating RALA/Au nanocomplexes to enhance nanoparticle internalisation efficiency, sensitising prostate tumour models to radiation treatment. J Nanobiotechnol 19, 279 (2021).