Tuning the cationic interface of simple polydiacetylene micelles to improve siRNA delivery at the cellular level

Hoang, Minh-Duc; Vandamme, Marie; Kratassiouk, Gueorgui; Pinna, Guillaume; Gravel, Edmond; Doris, Eric

doi:10.1039/c9na00571d

Cited by 8 publications

(4 citation statements)

References 43 publications

(25 reference statements)

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“…Liposomes represent successful delivery systems that have already made their way to the market as lipid-based siRNA delivery vectors siRNA viz. such as Lipofectamine, Oligofectamine, RNAifect, etc. have been applied for the delivery of siRNA.…”

Section: Introductionmentioning

confidence: 99%

Cyclo-RGD Truncated Polymeric Nanoconstruct with Dendrimeric Templates for Targeted HDAC4 Gene Silencing in a Diabetic Nephropathy Mouse Model

et al. 2020

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Diabetic nephropathy (DN), a chronic progressive kidney disease, is a significant complication of diabetes mellitus. Dysregulation of the histone deacetylases (HDACs) gene has been implicated in the pathogenesis of DN. Hence, the HDAC-inhibitors have emerged as a critical class of therapeutic agents in DN; however, the currently available HDAC4-inhibitors are mostly nonselective in nature as well as inhibit multiple HDACs. RNA interference of HDAC4 (HDAC4 siRNA) has shown immense promise, but the clinical translation has been impeded due to lack of a targeted, specific, and in vivo applicable delivery modality. In the present investigation, we examined Cyclo(RGDfC) (cRGD) truncated polymeric nanoplex with dendrimeric templates for targeted HDAC4 Gene Silencing. The developed nanoplex exhibited enhanced encapsulation of siRNA and offered superior protection against serum RNase nucleases degradation. The nanoplex was tested on podocytes (in vitro), wherein it showed selective binding to the αvβ3 integrin receptor, active cellular uptake, and significant in vitro gene silencing. The in vivo experiments showed remarkable suppression of the HDAC4 and inhibition in the progression of renal fibrosis in the Streptozotocin (STZ) induced DN C57BL/6 mice model. Histopathological and toxicological studies revealed nonsignificant abnormality/toxicity with the nanoplex. Conclusively, nanoplex was found as a promising tactic for targeted therapy of podocytes and could be extended for other kidney-related ailments.

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Section: Introductionmentioning

confidence: 99%

Cyclo-RGD Truncated Polymeric Nanoconstruct with Dendrimeric Templates for Targeted HDAC4 Gene Silencing in a Diabetic Nephropathy Mouse Model

et al. 2020

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“…Polydiacetylene micelles (pDA-micelles) have been thoroughly investigated by some of us as nanometric carriers for in vivo imaging 11 and drug delivery. 12 Compared to their non-polymerized counterparts, pDA-micelles are more stable, have higher loading capacity and exhibit reduced cytotoxicity (little to no effect on mitochondrial activity, membrane permeabilization, apoptosis/necrosis, secretion of pro-inflammatory cytokines or genotoxicity). 13 In addition, pDA-micelles are compact structures which may be advantageous with regard to diffusion and uptake into atherosclerotic plaques.…”

Section: Resultsmentioning

confidence: 99%

Targeted delivery of LXR-agonists to atherosclerotic lesions mediated by polydiacetylene micelles

Jamgotchian,

Devel,

Thai

et al. 2023

Nanoscale

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“…14 2.8. Micelles for siRNA transfection 15 In addition to conventional chemotherapeutics, small interfering RNAs (siRNAs) and their gene silencing properties have recently attracted attention for the treatment of diseases such as cancer. Therapeutic efficacy of siRNAs depends largely on their active transfection, as free nucleic acid do not freely pass cell membranes.…”

Section: Synlett Accountmentioning

confidence: 99%

Polydiacetylene Micelles in Nanomedicine and Beyond

Gravel,

Doris,

Demeese

2024

Synlett

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In this account article, we give an overview of our contribution to the development of stable micellar carriers obtained by self-assembly and photo-polymerization of diacetylenic amphiphiles. The stabilized micelles can be loaded with active substances and used for diagnostic and therapeutic applications, or loaded with a metal catalyst to promote some synthetic transformations in fully aqueous medium.

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Tuning the cationic interface of simple polydiacetylene micelles to improve siRNA delivery at the cellular level

Abstract: Polydiacetylene micelles, bearing different cationic head groups, were systematically investigated for their ability to efficiently deliver functional siRNAs to cells.

Cited by 8 publications

References 43 publications

Cyclo-RGD Truncated Polymeric Nanoconstruct with Dendrimeric Templates for Targeted HDAC4 Gene Silencing in a Diabetic Nephropathy Mouse Model

Cyclo-RGD Truncated Polymeric Nanoconstruct with Dendrimeric Templates for Targeted HDAC4 Gene Silencing in a Diabetic Nephropathy Mouse Model

Targeted delivery of LXR-agonists to atherosclerotic lesions mediated by polydiacetylene micelles

Polydiacetylene Micelles in Nanomedicine and Beyond

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