AI Article Synopsis
- Researchers developed a novel delivery system for siRNA using light-activated polyplexes to improve RNA interference therapy's effectiveness.
- The system combines sulfonated polyethylenimine with a photoactivatable component for controlled endosomal escape, which led to gene knock-down in cancer cells upon laser activation.
- While the sulfonated version needed light to function, the non-sulfonated version worked without additional treatment, suggesting different mechanisms of cellular release for the two approaches.
Article Abstract
Translation potential of RNA interference nanotherapeutics remains challenging due to in vivo off-target effects and poor endosomal escape. Here, we developed novel polyplexes for controlled intracellular delivery of dicer substrate siRNA, using a light activation approach. Sulfonated polyethylenimines covalently linked to pyropheophorbide-α for photoactivation and bearing modified amines (sulfo-pyro-PEI) for regulated endosomal escape were investigated. Gene knock-down by the polymer-complexed DsiRNA duplexes (siRNA-NPs) was monitored in breast cancer cells. Surprisingly, sulfo-pyro-PEI/siRNA-NPs failed to downregulate the PLK1 or eGFP proteins. However, photoactivation of these cell associated-polyplexes with a 661-nm laser clearly restored knock-down of both proteins. In contrast, protein down-regulation by non-sulfonated pyro-PEI/siRNA-NPs occurred without any laser treatments, indicating cytoplasmic disposition of DsiRNA followed a common intracellular release mechanism. Therefore, sulfonated pyro-PEI holds potential as a unique trap and release light-controlled delivery platform for on-demand gene silencing bearing minimal off target effects.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117728 | PMC |
| http://dx.doi.org/10.1016/j.nano.2020.102176 | DOI Listing |
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