Clickable polyethyleneimine incorporated into triblock copolymeric micelles as an efficient platform in the delivery of siRNA to NSCLC cells

Article Article scientifique Article Clickable polyethyleneimine incorporated into triblock copolymeric micelles as an efficient platform in the delivery of siRNA to NSCLC cells eng 2023-11-23 2024-01-05 author Marquet Franck Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, 1 Rue Michel Servet, 1211 Geneva, Switzerland; Section of Pharmaceutical Sciences, University of Geneva, 1 Rue Michel Servet, 1211 Geneva, Switzerland. 727220 author Hagen Harry Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, 1 Rue Michel Servet, 1211 Geneva, Switzerland; Section of Pharmaceutical Sciences, University of Geneva, 1 Rue Michel Servet, 1211 Geneva, Switzerland. 780680 author Stanchieri Mattia Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, 1 Rue Michel Servet, 1211 Geneva, Switzerland; Section of Pharmaceutical Sciences, University of Geneva, 1 Rue Michel Servet, 1211 Geneva, Switzerland. 951016 author Serre Beinier Véronique 0000-0002-6016-1645 Division of Thoracic and Endocrine Surgery, University Hospitals and University of Geneva, Switzerland. 123229 Département de chirurgie (CHIRU) author Grasso Gianvito Dalle Molle Institute for Artificial Intelligence (IDSIA), University of Italian Switzerland (USI), University of Applied Science and Art of Southern Switzerland (SUPSI), Polo Universitario Lugano - Campus Est, Via la Santa 1 CH-6962, Lugano-Viganello, Switzerland. author Danani Andrea Dalle Molle Institute for Artificial Intelligence (IDSIA), University of Italian Switzerland (USI), University of Applied Science and Art of Southern Switzerland (SUPSI), Polo Universitario Lugano - Campus Est, Via la Santa 1 CH-6962, Lugano-Viganello, Switzerland. author Patrulea Viorica Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, 1 Rue Michel Servet, 1211 Geneva, Switzerland; Section of Pharmaceutical Sciences, University of Geneva, 1 Rue Michel Servet, 1211 Geneva, Switzerland. 813295 Section des sciences pharmaceutiques (FARMA) author Borchard Gerrit 0000-0001-6268-2586 Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, 1 Rue Michel Servet, 1211 Geneva, Switzerland; Section of Pharmaceutical Sciences, University of Geneva, 1 Rue Michel Servet, 1211 Geneva, Switzerland. Electronic address: Gerrit.Borchard@unige.ch. 635281 Section des sciences pharmaceutiques (FARMA) 123632 10.1016/j.ijpharm.2023.123632 38000648 0378-5173 https://www.sciencedirect.com/science/article/pii/S0378517323010542 The efficacy of transfection vectors to cross the endosomal membrane into the cytosol is a central aspect in the development of nucleic acid-based therapeutics. The challenge remains the same: Delivery, Delivery, Delivery. Despite a rational and appropriate construct of triblock polymeric micelles, which could serve as an ideal platform for the co-delivery of siRNAs and hydrophobic anticancer drugs, we show here its inability to properly convey oligonucleotides to their final destination. In order to overcome biological barriers, a linear PEI comprising two orthogonal groups was synthesized, holding an appropriate balance between safety and efficacy. Micellar carriers were then formulated with this polymer to enhance endosomal siRNA release. This chemical technology also addresses the two major challenges to consider when developing novel micellar products for siRNA delivery, namely cytotoxicity of polycations and endosomal escape. Herein, we demonstrate successful release of siRNA using a polymer tailoring strategy combined with a relevant in vitro approach, considering STAT3 as a promising target in the treatment of non-small cell lung cancer (NSCLC). Endosomal escape Lung cancer Polyethylenimine SiRNA delivery Humans RNA, Small Interfering / chemistry Carcinoma, Non-Small-Cell Lung / genetics Carcinoma, Non-Small-Cell Lung / therapy Polyethyleneimine / chemistry Micelles Lung Neoplasms / genetics Polymers / chemistry Cell Line, Tumor Dewey 610 Dewey 615 Dewey 617 31 Section des sciences pharmaceutiques 17 4f7589ed-e44d-4850-a4d8-b0c1eccdfe48 Centre de recherche translationnelle en onco-hématologie 209 57 Département de chirurgie 222 false 902 Cancer du poumon et mésothéliome pleural malin 944 879 Biopharmacie International journal of pharmaceutics 649 8f45c3f6-4dba-4a3a-94d9-175c2f00bcf4 Article (Published version) Public Marquet_F_et_al_International_Journ.pdf 3642039 application/pdf CC BY-4.0 754735a69b53ec1f2592f9b5ffbb94bb1d16bede0b4c4174d9c20931649a840e f9589dc5-f9d2-4d7d-87de-b8aff5e9f9a9 Supplemental data Public 1-s2.0-S0378517323010542-mmc1.docx 8493171 application/vnd.openxmlformats-officedocument.wordprocessingml.document 832895dc9e299b73d086eefe9c53dedef3df9ff189abe03484beb2b06649dc40 Vignette Public 1-s2.0-S0378517323010542-ga1_lrg.jpg 224304 image/png openAccess Faculté des sciences / Section des sciences pharmaceutiques Faculté de médecine / Centre de recherche translationnelle en onco-hématologie Faculté de médecine / Section de médecine clinique / Département de chirurgie

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Clickable polyethyleneimine incorporated into triblock copolymeric micelles as an efficient platform in the delivery of siRNA to NSCLC cells	International journal of pharmaceutics			2024	6	6

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Hagen, Harry