Hypoxia-Responsive Copolymer for siRNA Delivery

Federico Perche (1) , Swati Biswas (1) , Niravkumar Patel (1) , Vladimir Torchilin (1)

1 Northeastern University [Boston]

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.

Mots clés: Azobenzene; Stimuli-sensitive; Tumor hypoxia; Tumor targeting; siRNA delivery

Domaines: Sciences du Vivant [q-bio]

Federico Perche, Swati Biswas, Niravkumar Patel, Vladimir Torchilin. Hypoxia-Responsive Copolymer for siRNA Delivery. Methods in Molecular Biology, 2016, 1372 : RNA Imaging, pp.139-162. ⟨10.1007/978-1-4939-3148-4_12⟩. ⟨hal-02130872⟩