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

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http://hdl.handle.net/10138/336327

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Kadekar , S , Nawale , GN , Rangasami , VK , Le Joncour , V , Laakkonen , P , Hilborn , J , Varghese , OP & Oommen , OP 2021 , ' Redox responsive Pluronic micelle mediated delivery of functional siRNA: a modular nano-assembly for targeted delivery ' , Biomaterials Science , vol. 9 , no. 11 , pp. 3939-3944 . https://doi.org/10.1039/d1bm00428j

Title: Redox responsive Pluronic micelle mediated delivery of functional siRNA: a modular nano-assembly for targeted delivery
Author: Kadekar, S; Nawale, GN; Rangasami, VK; Le Joncour, V; Laakkonen, P; Hilborn, J; Varghese, OP; Oommen, OP
Contributor organization: CAN-PRO - Translational Cancer Medicine Program
Doctoral Programme in Biomedicine
Helsinki Institute of Life Science HiLIFE, Infra
Pirjo Maarit Laakkonen / Principal Investigator
Biosciences
Translational Cancer Biology (TCB) Research Programme
Research Programs Unit
Date: 2021-06
Language: eng
Number of pages: 6
Belongs to series: Biomaterials Science
ISSN: 2047-4830
DOI: https://doi.org/10.1039/d1bm00428j
URI: http://hdl.handle.net/10138/336327
Abstract: 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.
Subject: SIDE-CHAINS
DNA
TRANSFECTION
VECTOR
CELLS
STAT3
3111 Biomedicine
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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