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: Federico Perche, Swati Biswas, Niravkumar R Patel, Vladimir P Torchilin
• Journal: Methods in molecular biology (Clifton, N.J.) (Methods Mol Biol) Vol. 1372 Pg. 139-62 ( 2016) ISSN: 1940-6029 [Electronic] United States
• PMID: 26530922 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Polymers
• RNA, Small Interfering
• Polyethylene Glycols
• Polyethyleneimine

Topics

• Animals
• Cell Culture Techniques
• Cell Hypoxia
• Cell Line, Tumor
• Disease Models, Animal
• Female
• Flow Cytometry
• Gene Expression
• Gene Silencing
• Gene Transfer Techniques
• Genes, Reporter
• Heterografts
• Humans
• Hypoxia (metabolism)
• Melanoma, Experimental
• Mice
• Microscopy, Fluorescence (methods)
• Neoplasms (diagnosis, genetics)
• Polyethylene Glycols (chemistry)
• Polyethyleneimine (chemistry)
• Polymers (chemistry)
• RNA Interference
• RNA, Small Interfering (chemistry, genetics, metabolism)
• Tissue Distribution