targeted crm197-peg-peisirna complexes for therapeutic rnai in glioblastoma针对crm197-peg-peisirna复合物治疗rnai胶质母细胞瘤.pdf

Pharmaceuticals 2011, 4, 1591-1606; doi:10.3390/ph4121591 OPEN ACCESS Pharmaceuticals ISSN 1424-8247 /journal/pharmaceuticals Article Targeted CRM197-PEG-PEI/siRNA Complexes for Therapeutic RNAi in Glioblastoma Sabrina Höbel 1,2, Chantal C.M. Appeldoorn 3, Pieter J. Gaillard 3 and Achim Aigner 1,2,* 1 Institute of Pharmacology/Biochemical-Pharmacological Center (bpc), Faculty of Medicine, Philipps-University Marburg, Karl-von-Frisch-Strasse 1, D-35032 Marburg, Germany 2 Rudolf-Boehm-Institute of Pharmacology and Toxicology, Clinical Pharmacology, Härtelstrasse 16-18, D-04107 Leipzig, Germany 3 to-BBB technologies BV, Bio Partner Center II, Niels Bohrweg 11, 2333 CA Leiden, The Netherlands; E-Mail: PieterGaillard@toBBB.com (P.J.G.) * Author to whom correspondence should be addressed; E-Mail: achim.aigner@medizin.uni-leipzig.de; Tel.: +49-341-972-4661, Fax: +49-341-972-4669. Received: 16 September 2011; in revised form: 8 December 2011 / Accepted: 9 December 2011 / Published: 16 December 2011 Abstract: RNA interference (RNAi) allows the specific knockdown of tumor relevant genes. To induce RNAi, the delivery of small interfering RNAs (siRNAs) is of crucial importance. This is particularly challenging for their therapeutic applications in vivo. Low molecular weight branched polyethylenimine (PEI) is safe and efficient for nucleic acid delivery including small RNA molecules, based on its ability to electrostatically complex siRNA molecules, thereby protecting them from