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Hypoxia-Responsive Copolymer for siRNA Delivery

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RNA Imaging

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1372))

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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Acknowledgments

This work was supported by grant U54CA151881 to Pr. Torchilin.

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Authors and Affiliations

  1. Center for Pharmaceutical Biotechnology and Nanomedicine, School of Pharmacy, Bouve College of Health Sciences, Northeastern University, Boston, MA, USA

    Federico Perche, Swati Biswas, Niravkumar R. Patel & Vladimir P. Torchilin Ph.D., D.Sc.

  2. Department of Pharmaceutical Sciences, School of Pharmacy, Bouve College of Health Sciences, Northeastern University, Boston, MA, USA

    Federico Perche, Swati Biswas & Niravkumar R. Patel

  3. Department of Pharmaceutical Sciences, School of Pharmacy, Bouve College of Health Sciences, Northeastern University, 140 The Fenway, room 214, 360 Huntington Avenue, Boston, 02129, MA, USA

    Vladimir P. Torchilin Ph.D., D.Sc.

Authors
  1. Federico Perche
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  2. Swati Biswas
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  3. Niravkumar R. Patel
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  4. Vladimir P. Torchilin Ph.D., D.Sc.
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Correspondence to Vladimir P. Torchilin Ph.D., D.Sc. .

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Editors and Affiliations

  1. Massachusetts General Hospital, Charlestown, Massachusetts, USA

    Zdravka Medarova

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Perche, F., Biswas, S., Patel, N.R., Torchilin, V.P. (2016). Hypoxia-Responsive Copolymer for siRNA Delivery. In: Medarova, Z. (eds) RNA Imaging. Methods in Molecular Biology, vol 1372. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3148-4_12

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  • DOI: https://doi.org/10.1007/978-1-4939-3148-4_12

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-3147-7

  • Online ISBN: 978-1-4939-3148-4

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