Chitosan/dsRNA polyplex nanoparticles advance environmental RNA interference efficiency through activating clathrin-dependent endocytosis

Zhou, Hong; Wan, Fenglin; Jian, Yufan; Guo, Fuyou; Zhang, Miao; Shi, Shiyao; Yang, Liang; Li, Shili; Liu, Ying; Ding, Wei

doi:10.1016/j.ijbiomac.2023.127021

Cited by 10 publications

(1 citation statement)

References 60 publications

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“…4 ). Well-documented endocytosis and active transport inhibitors were used to investigate the cellular uptake mechanisms [ 49 ]. It is verified that a soluble compound BN1 with one quaternary ammonium salt group enables efficient penetration of the BBB via microtubule-mediated transcytosis (Fig.…”

Section: Discussionmentioning

confidence: 99%

Advancing Central Nervous System Drug Delivery with Microtubule-Dependent Transcytosis of Novel Aqueous Compounds

Zhang,

Zhong,

et al. 2024

Biomater Res

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The challenge of delivering therapeutics to the central nervous system due to the restrictive nature of the blood–brain barrier (BBB) is a substantial hurdle in neuropharmacology. Our research introduces a breakthrough approach using microtubule-dependent transcytosis facilitated by novel aqueous compounds. We synthesized a series of red-emitting pyran nitrile derivatives. The molecular structure of compounds, photophysical properties, and water solubility were characterized. BBB permeability of BN1 was assessed in an in vitro BBB model. The transmembrane transport mechanism was next analyzed. The derivative was injected in the wild-type mouse for evaluation of brain penetration and biodistribution in the brain. We further investigated the potential of BN1-functionalized BBB-nonpenetrated silica nanoparticles for brain targeting. This compound demonstrated an ability to form endosomes within the phospholipid layer, thus enabling efficient penetration of the BBB via microtubule-mediated transcytosis, as evidenced in vitro model. This was further confirmed by in vivo experiments that BN1 displays the excellent BBB penetration and retained in brain parenchyma. Furthermore, BBB-impermeable mesoporous silica nanoparticle codelivery system markedly enhanced the transport efficiency to the brain in vivo by BN1-functionalized. These findings indicate that our designed aqueous molecules not only are capable of traversing the BBB but also serve as a viable new strategy for central-nervous-system-targeted drug delivery.

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Section: Discussionmentioning

confidence: 99%

Advancing Central Nervous System Drug Delivery with Microtubule-Dependent Transcytosis of Novel Aqueous Compounds

Zhang,

Zhong,

et al. 2024

Biomater Res

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Evaluation of non-invasive dsRNA delivery methods for the development of RNA interference in the Asian tiger mosquito Aedes albopictus

Girard,

Berthaud,

Martin

et al. 2024

J Pest Sci

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The Asian tiger mosquito Aedes albopictusis one of the most invasive species and an e cient vector of several pathogens. RNA interference (RNAi) has been proposed as an alternative method to control mosquito populations by silencing the expression of genes that are essential for their survival. However, the optimal delivery method for dsRNAs to enhance an optimal RNAi remains elusive and comparative studies are lacking. We have, therefore, compared the e ciency of three non-invasive delivery methods to mosquito larvae: soaking, rehydration and nanoparticle ingestion. Each method was tested separately on four genes predicted to code non-essential proteins (i.e. collagenase-like, kynurenine 3-monooxygenaselike, yellow-like and venom serine protease-like) in order to be able to compare the importance of gene knock-down.All tested methods successfully downregulated mosquito gene expression. However, silencing e ciency strongly varies among methods and genes. Silencing (95.1%) was higher for Kynurenine 3monooxygenase-like with rehydration and nanoparticle ingestion (61.1%). For the Venom serine proteaselike, the most e cient silencing was observed with soaking (74.5%) and rehydration (34%). In contrast, the selected methods are ine cient to silence the other genes. Our ndings also indicate that gene copy numbers, transcript sizes and GC content correlate with the silencing e ciency.From our results, rehydration was the most speci c and e cient methods to speci cally knock-down gene expression in Ae. albopictus larvae. Nevertheless, considering the observed variability of e ciency is gene-dependent, our results also point at the necessity to test and optimize diverse dsRNA delivery approaches to achieve a maximal RNAi e ciency. Key MessageRNA interference (RNAi) of essential genes has been proposed to help basic research and insecticides production.Optimal noninvasive delivery methods of dsRNA to induce RNAi still needs to be determined.In this study we showed that an osmotic stress can increase the RNAi e ciency.Genes characteristics (copy numbers, transcript sizes and GC content) correlated with the silencing e ciency.

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DsRNA-based pesticides: Considerations for efficiency and risk assessment

Dalakouras,

Koidou,

Papadopoulou

2024

Chemosphere

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Chitosan/dsRNA polyplex nanoparticles advance environmental RNA interference efficiency through activating clathrin-dependent endocytosis

Cited by 10 publications

References 60 publications

Advancing Central Nervous System Drug Delivery with Microtubule-Dependent Transcytosis of Novel Aqueous Compounds

Advancing Central Nervous System Drug Delivery with Microtubule-Dependent Transcytosis of Novel Aqueous Compounds

Evaluation of non-invasive dsRNA delivery methods for the development of RNA interference in the Asian tiger mosquito Aedes albopictus

DsRNA-based pesticides: Considerations for efficiency and risk assessment

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