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

Sandeep Kadekar, Ganesh N. Nawale, Vignesh K. Rangasami, Vadim Le Joncour, Pirjo Laakkonen, Jöns Hilborn, Oommen P. Varghese, Oommen P. Oommen

Research output: Contribution to journalArticleScientificpeer-review

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 ∼291 nm in DLS and ∼200-250 nm in SEM at 37 °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 ∼65% silencing of STAT3 mRNA in BT-13 gliospheres, while only ∼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.

Original languageEnglish
Pages (from-to)3939-3944
Number of pages6
JournalBiomaterials Science
Volume9
Issue number11
DOIs
Publication statusPublished - 2021
Publication typeA1 Journal article-refereed

Publication forum classification

  • Publication forum level 1

ASJC Scopus subject areas

  • Biomedical Engineering
  • Materials Science(all)

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