title: Hypoxia-Responsive Copolymer for siRNA Delivery.
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.
authors.affiliation: Center for Pharmaceutical Biotechnology and Nanomedicine, School of Pharmacy, Bouve College of Health Sciences, Northeastern University, Boston, MA, USA.|Department of Pharmaceutical Sciences, School of Pharmacy, Bouve College of Health Sciences, Northeastern University, Boston, MA, USA.
authors.forename: Federico
authors.initials: F
authors.lastname: Perche
authors.affiliation: Center for Pharmaceutical Biotechnology and Nanomedicine, School of Pharmacy, Bouve College of Health Sciences, Northeastern University, Boston, MA, USA.|Department of Pharmaceutical Sciences, School of Pharmacy, Bouve College of Health Sciences, Northeastern University, Boston, MA, USA.
authors.forename: Swati
authors.initials: S
authors.lastname: Biswas
authors.affiliation: Center for Pharmaceutical Biotechnology and Nanomedicine, School of Pharmacy, Bouve College of Health Sciences, Northeastern University, Boston, MA, USA.|Department of Pharmaceutical Sciences, School of Pharmacy, Bouve College of Health Sciences, Northeastern University, Boston, MA, USA.
authors.forename: Niravkumar R
authors.initials: NR
authors.lastname: Patel
authors.affiliation: Center for Pharmaceutical Biotechnology and Nanomedicine, School of Pharmacy, Bouve College of Health Sciences, Northeastern University, Boston, MA, USA. v.torchilin@neu.edu.|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. v.torchilin@neu.edu.
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Torchilin
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D020868:Gene Silencing; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D064593:Heterografts; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D008546:Melanoma, Experimental; D051379:Mice; D008856:Microscopy, Fluorescence / Q000379:methods; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics; D011092:Polyethylene Glycols / Q000737:chemistry; D011094:Polyethyleneimine / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D011108:Polymers; D034741:RNA, Small Interfering; D011092:Polyethylene Glycols; D011094:Polyethyleneimine
keywords: Azobenzene; Stimuli-sensitive; Tumor hypoxia; Tumor targeting; siRNA delivery