Redox responsive Pluronic micelle mediated delivery of functional siRNA: a modular nano-assembly for targeted delivery

Kadekar, SandeepUppsala universitet,Polymerkemi,sandeep.kadekar@kemi.uu.se (författare)

Redox responsive Pluronic micelle mediated delivery of functional siRNA : a modular nano-assembly for targeted delivery

There is an unmet need to develop strategies that allow site-specific delivery of short interfering RNA (siRNA) without any associated toxicity. To address this challenge, we have developed a novel siRNA delivery platform using chemically modified pluronic F108 as an amphiphilic polymer with a releasable bioactive disulfide functionality. The micelles exhibited thermoresponsive properties and showed a hydrodynamic size of similar to 291 nm in DLS and similar to 200-250 nm in SEM at 37 degrees C. The grafting of free disulfide pyridyl groups enhanced the transfection efficiency and was successfully demonstrated in human colon carcinoma (HCT116; 88%) and glioma cell lines (U87; 90%), non-cancerous human dermal fibroblast (HDF; 90%) cells as well as in mouse embryonic stem (mES; 54%) cells. To demonstrate the versatility of our modular nanocarrier design, we conjugated the MDGI receptor targeting COOP peptide on the particle surface that allowed the targeted delivery of the cargo molecules to human patent-derived primary BT-13 gliospheres. Transfection experiments with this design resulted in similar to 65% silencing of STAT3 mRNA in BT-13 gliospheres, while only similar to 20% of gene silencing was observed in the absence of the peptide. We believe that our delivery method solves current problems related to the targeted delivery of RNAi drugs for potential in vivo applications.

Nawale, Ganesh N.Uppsala universitet,Polymerkemi(Swepub:uu)ganna194 (författare)
Rangasami, Vignesh K.Uppsala universitet,Polymerkemi,Tampere Univ, Fac Med & Hlth Technol, Bioengn & Nanomed Grp, Tampere 33720, Finland.(Swepub:uu)vigra621 (författare)
Le Joncour, VadimUniv Helsinki, Translat Canc Med Res Program, Fac Med, Helsinki, Finland. (författare)
Laakkonen, PirjoUniv Helsinki, Translat Canc Med Res Program, Fac Med, Helsinki, Finland. (författare)
Hilborn, Jöns,1956-Uppsala universitet,Polymerkemi,Uppsala Univ, Dept Chem, Polymer Chem, Angstrom Lab, S-75121 Uppsala, Sweden.(Swepub:uu)johil255 (författare)
Varghese, Oommen P.,1977-Uppsala universitet,Polymerkemi(Swepub:uu)oopva021 (författare)
Oommen, Oommen P.Tampere Univ, Fac Med & Hlth Technol, Bioengn & Nanomed Grp, Tampere 33720, Finland. (författare)
Uppsala universitetPolymerkemi (creator_code:org_t)

Ingår i:Biomaterials Science: Royal Society of Chemistry9:11, s. 3939-39442047-48302047-4849

Av författaren/redakt...: Kadekar, Sandeep; Nawale, Ganesh N ...; Rangasami, Vigne ...; Le Joncour, Vadi ...; Laakkonen, Pirjo; Hilborn, Jöns, 1 ...; visa fler...; Varghese, Oommen ...; Oommen, Oommen P ...; visa färre...

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