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iRGD peptide conjugation potentiates intraperitoneal tumor delivery of paclitaxel with polymersomes

Simon-Gracia, Lorena and Hunt, Hedi and Scodeller, Pablo and Gaitzsch, Jens and Kotamraju, Venkata Ramana and Sugahara, Kazuki N. and Tammik, Olav and Ruoslahti, Erkki and Battaglia, Giuseppe and Teesalu, Tambet. (2016) iRGD peptide conjugation potentiates intraperitoneal tumor delivery of paclitaxel with polymersomes. Biomaterials, 104. pp. 247-257.

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Official URL: http://edoc.unibas.ch/52108/

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Abstract

Polymersomes are versatile nanoscale vesicles that can be used for cytoplasmic delivery of payloads. Recently, we demonstrated that pH-sensitive polymersomes exhibit an intrinsic selectivity towards intraperitoneal tumor lesions. A tumor homing peptide, iRGD, harbors a cryptic C-end Rule (CendR) motif that is responsible for neuropilin-1 (NRP-1) binding and for triggering extravasation and tumor penetration of the peptide. iRGD functionalization increases tumor selectivity and therapeutic efficacy of systemic drug-loaded nanoparticles in many tumor models. Here we studied whether intraperitoneally administered paclitaxel-loaded iRGD-polymersomes show improved efficacy in the treatment of peritoneal carcinomatosis. First, we demonstrated that the pH-sensitive polymersomes functionalized with RPARPAR (a prototypic CendR peptide) or iRGD internalize in the cells that express NRP-1, and that internalized polymersomes release their cargo inside the cytosol. CendR-targeted polymersomes loaded with paclitaxel were more cytotoxic on NRP-1-positive cells than on NRP-1-negative cells. In mice bearing peritoneal tumors of gastric (MKN-45P) or colon (CT26) origin, intraperitoneally administered RPARPAR and iRGD-polymersomes showed higher tumor-selective accumulation and penetration than untargeted polymersomes. Finally, iRGD-polymersomes loaded with paclitaxel showed improved efficacy in peritoneal tumor growth inhibition and in suppression of local dissemination compared to the pristine paclitaxel-polymersomes or Abraxane. Our study demonstrates that iRGD-functionalization improves efficacy of paclitaxel-polymersomes for intraperitoneal treatment of peritoneal carcinomatosis.
Faculties and Departments:05 Faculty of Science > Departement Chemie
05 Faculty of Science > Departement Chemie > Chemie > Makromolekulare Chemie (Meier)
UniBasel Contributors:Meier, Wolfgang P.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Elsevier
ISSN:0142-9612
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:23 Jan 2017 15:06
Deposited On:23 Jan 2017 15:06

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