A new discovery platform for RNA delivery vehicles could mean 20 per cent more efficiency for guiding nanoparticles into cancer cells, say researchers.
The team, led by Harvard Medical School’s Omid Farokhzad, took folded RNA (ribonucleic acid) strands – known as aptamers – to target prostate cancer cells ligands, and loaded them with cancer drug docetaxel.
However the researchers focussed on developing not only a means of targeting the ligands, but also a way of directing the nanoparticles straight into the cells before releasing the medication.
Farokhzad branded traditional targeted nanoparticle (NP) therapeutics studies as “inefficient” because they often rely on diffusion into the membrane once the target cells are reached, rather than entering the cell directly.
He attributed this largely to other research utilising only a limited number of well-characterised antigens which are not always effective in entering their intended cells.
“People have been interested in getting nanoparticles into cells for a while now,” Farokhzad told in-PharmaTechnologist. “The novelty of our study is that the ligand was selected by virtue of how well they were internalised.”
He told us the team realised the missing element in developing targeted nanoparticle was internalising ligands, because though getting nanoparticles to attach to cells then permeate the membrane works, it isn’t as effective as it could be.
“The problem is, these ligands are very hard to find,” he said, “so we developed a platform that could do this.”
Instead, Farokhzad's team hypothesized that a “robust targeted internalizing NP delivery platform needs to be established where development can be achieved without pre-characterization of target antigens.”
To achieve this goal, the scientists designed a unique selection strategy to enrich internalising aptimers for NP incorporation.
The selection process first incubated more than 100 trillion aptamers with live cancer cells, discarding those that did not interact with the target cells. The process was repeated eleven times, in a survival of the fittest process.
Among the more than 30 isolated aptamers left, only one was reported to have the internalization feature – known as XEO2 mini.
The team then treated the prostate cancer cells with the selected drug-loaded nanoparticles, and found the NPs with XE02 mini had over 20 per cent more efficiency than those without.
Now the researchers plan to test the treatment in animal models.
In the paper, titled Engineering of Targeted Nanoparticles for Cancer Therapy Using Internalizing Aptamers Isolated by Cell-Uptake Selection , Farokhzad wrote that the novel selection process could be used to create better delivery vehicles for a “myriad of other diseases”.
“I think it alerts all of us to the fact that we are able to create internalising ligands that can potentially open new doors in the way we engineer and design antibody drug conjugates or targeted nano drug platforms, and make them more effective,” he told in-PharmaTechnologist.
He added that the simplified process of targeted NP development – which eliminates the need for detailed knowledge of target antigens on cell surface – could also be used in similar uptake selection studies for delivering various molecules, including drugs and siRNAs, into target cells.