Thermo-triggered release of a genome-editing machinery by modified gold nanoparticles for tumor therapy.

‘Gold nanoparticles, peptides, and lipids assembled into a sophisticated multifunctional carrier/release system could serve as a multifunctional delivery platform for various aspects of gene therapy.’

Gold nanoparticles are especially attractive carriers for various biological molecules because of their easy modification, stability, and light-irradiation response. To convert them into a versatile biological transport and delivery vehicle, the scientists first attached Tat peptides--which facilitate the crossing of the cell nucleus membrane--to gold nanoparticles. Then, the CRISPR-Cas9 plasmid containing the RNA targeting the Plk-1 gene--the knockout of which would severely impair tumor cell function--was attached to the Tat peptides through electrostatic interactions so that they would release their load right after entering the nucleus. Finally, the nanoparticular system was coated with a formulation of lipids to improve cellular uptake. 




To test the system, cells and tumor-bearing mice were both administrated with the CRISPR-Cas9-plasmid-carrying nanogold vehicle, and the release of the gene-editing machine was triggered by a laser. "In this study, light irradiation caused the release of the Tat peptide from the gold nanoparticles in a time- and laser-intensity-dependent manner," the authors explained. Other approaches are also possible as they pointed out: as the gold nanoparticles heat up upon irradiation, they could serve as thermotherapeutic agents themselves. In summary, this relatively simple design entailing gold nanoparticles, peptides, and lipids assembled into a sophisticated multifunctional carrier/release system could serve as a multifunctional delivery platform for various aspects of gene therapy.
Source-Eurekalert