DNA nanostructures are extremely advantageous gene carriers in nanomedicine applications, but their delivery efficiency to the nucleus is still very low. Recently, a scientific research team at the University of Chinese in Hong Kong proposed an intracellular mechanical transmission path for DNA nanostructures, and the relevant results were published online in Nano Communications on April 18.
In the study, the team proposed the application of extracellular mechanical stimulation to activate cell mechanical conduction and promote intranuclear transmission of DNA nanostructures.
Specifically, mammalian cells are treated with polythymic pyrimidine-rich spherical nucleic acids (poly(T)SNAs) under gentle compression of a single coverslip, which produces high nuclear buildup without serious endosome inclusion, cytotoxicity, or long-term membrane damage; this method does not require chemical modification or transfection reagents.
The study found that a slight squeeze activates the mechanical conduction of DNA nanostructures and causes nuclear displacement. Combined with compression and poly-oligonucleotide therapy, genes associated with myosin, actin filaments, and nuclear input can be upregulated. Compressing endothelioma cells with spherical nucleic acids containing antisense oligonucleotides inhibits the growth of intranuclear oncogenes.
External forces promote the transmission of DNA nanostructures within the nucleus In the picture from the paper
The research team said that this research result will promote the fusion application of DNA nanotechnology and cell biomechanics in intranuclear research. (Source: China Science Daily Zheng Jinwu)
Related paper information:https://doi.org/10.1021/acs.nanolett.2c00667