RESUMEN
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.
Asunto(s)
Neoplasias de la Mama/genética , Proteínas de Ciclo Celular/genética , ARN Helicasas DEAD-box/genética , Silenciador del Gen , Proteínas Serina-Treonina Quinasas/genética , Proteínas Proto-Oncogénicas/genética , Ribonucleasa III/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Línea Celular Tumoral , Endosomas/efectos de los fármacos , Femenino , Técnicas de Silenciamiento del Gen , Proteínas Fluorescentes Verdes/genética , Humanos , Polietileneimina/química , Polietileneimina/farmacología , Polímeros/química , Interferencia de ARN , ARN Interferente Pequeño/farmacología , Quinasa Tipo Polo 1RESUMEN
Artisanal and small-scale gold mining (ASGM) is the primary global source of anthropogenic mercury (Hg) emissions and a large source of landscape change. ASGM occurs throughout the world, including in the Peruvian Amazon. This data set contains measurements of surface water, precipitation, throughfall, leaves, sediment, soil, and air samples from across the Madre de Dios region of Peru, in locations near and remote from ASGM. These data were collected to determine the fate and transport of Hg across the landscape. Samples were collected in 2018 and 2019. Data predominantly included total Hg and methyl Hg concentrations in surface water, precipitation, throughfall, leaves, sediment, soil, and air. Additional water and soil parameters were also measured to better characterize their chemistry. There are no copyright restrictions; please cite this data paper when the data are used in publication.