High-throughput nanoparticle screening propels RNA drug delivery to clinical settings

Aided by their role in today’s SARS-CoV-2 messenger RNA vaccines, nanoparticles gained prominence in the world of drug delivery. Identifying optimal formulations of these molecules historically required time-intensive approaches aimed at making slight modifications to pre-existing formulations.

Tomé et al. take stock of the burgeoning use of high-throughput techniques for developing drug delivery systems. By enhancing molecular targeting and release kinetics, high-throughput workflows have made it more feasible to develop ways to deliver several new types of biomolecules, namely mRNA, small interfering RNAs and microRNAs.

“The manuscript celebrates 20 years of research in high-throughput screening of nanoparticles in drug delivery after the initial report in 2001,” said author Inês Tomé.

High-throughput synthesis focuses on forming large numbers of nanoparticles, followed by library screening to identified “hits” that affect the target in the desired way.

Single-cell transcriptomics and proteomics are poised to provide a cost-effective method for assessing cellular responses to the RNA libraries. The cost of such techniques dropped to 1 cent per cell, allowing millions of cells to be sampled per experiment.

Tomé looks to continue tackling a major hurdle for the field: overcoming barriers posed by blood vessels, namely the blood-brain barrier.

“We are particularly interested in developing nanoformulations with the capacity to target specific organs/tissues such as the heart and the brain,” she said. “These two organs are very difficult to target, because once the nanoformulations are administered in the bloodstream, most of them are retained by the liver and kidney.”

Source: “High-throughput screening of nanoparticles in drug delivery,” by Inês Tomé, Vitor Francisco, Hugo Fernandes, and Lino Ferreira, APL Bioengineering (2021). The article can be accessed at https://doi.org/10.1063/5.0057204 .