Chapter title |
Hypoxia-Responsive Copolymer for siRNA Delivery.
|
---|---|
Chapter number | 12 |
Book title |
RNA Imaging
|
Published in |
Methods in molecular biology, January 2016
|
DOI | 10.1007/978-1-4939-3148-4_12 |
Pubmed ID | |
Book ISBNs |
978-1-4939-3147-7, 978-1-4939-3148-4
|
Authors |
Perche, Federico, Biswas, Swati, Patel, Niravkumar R, Torchilin, Vladimir P, Federico Perche, Swati Biswas, Niravkumar R. Patel, Vladimir P. Torchilin Ph.D., D.Sc., Vladimir P. Torchilin |
Editors |
Zdravka Medarova |
Abstract |
A wide variety of nanomedicine has been designed for cancer therapy. Herein, we describe the synthesis and evaluation of a hypoxia-responsive copolymer for siRNA delivery (Perche et al., Angew Chem Int Ed Engl 53:3362-3366, 2014). The synthesis is achieved using established coupling chemistry and accessible purification procedures. A polyelectrolyte-lipid conjugate (polyethyleneimine 1.8 kDa-dioleyl-phosphatidylinositol, PEI-PE) and polyethylene glycol 2000 (PEG) were assembled via the hypoxia-sensitive azobenzene (Azo) unit to obtain the PEG-Azo-PEI-DOPE copolymer. This copolymer can condense siRNA and shows hypoxia-induced cellular internalization and reporter gene downregulation in vitro and tumor accumulation in vivo after parenteral administration (Perche et al., Angew Chem Int Ed Engl 53:3362-3366, 2014). We also detail procedures to evaluate hypoxia-targeted polymers both in monolayer cultures, cancer cell spheroids and in tumor xenografts murine models. |
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