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

文献信息

发布日期 2021-05-04

DOI 10.1039/D1BM00428J

影响因子 6.843

作者

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

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摘要

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.

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来源期刊

Biomaterials Science

CiteScore: 11.5

自引率: 3.4%

年发文量: 492

Biomaterials Science is an international high impact journal exploring the science of biomaterials and their translation towards clinical use. Its scope encompasses new concepts in biomaterials design, studies into the interaction of biomaterials with the body, and the use of materials to answer fundamental biological questions. Papers do not necessarily need to report a new biomaterial but should provide novel insight into the biological applications of the biomaterial. Articles that primarily focus on demonstrating novel materials chemistry and bring a molecular picture to bear on a given material’s suitability as a biomaterial are more suited to our companion journal, Journal of Materials Chemistry B. Biomaterials Science publishes primary research and review-type articles in the following areas: molecular design of biomaterials, including translation of emerging chemistries to biomaterials science of cells and materials at the nanoscale and microscale materials as model systems for stem cell and human biology materials for tissue engineering and regenerative medicine (Nano)materials and (nano)systems for therapeutic delivery interactions at the biointerface biologically inspired and biomimetic materials, including bio-inspired self-assembly systems and cell-inspired synthetic tools next-generation biomaterials tools and methods