Simon-Gracia, L;
Hunt, H;
Scodeller, P;
Gaitzsch, J;
Kotamraju, VR;
Sugahara, KN;
Tammik, O;
... Teesalu, T; + view all
(2016)
iRGD peptide conjugation potentiates intraperitoneal tumor delivery of paclitaxel with polymersomes.
Biomaterials
, 104
pp. 247-257.
10.1016/j.biomaterials.2016.07.023.
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Simon-Gracia et al iRGD peptide conjugation potentiates intraperitoneal tumor delivery of paclitaxel with polymersomes.pdf Download (1MB) | Preview |
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.
Type: | Article |
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Title: | iRGD peptide conjugation potentiates intraperitoneal tumor delivery of paclitaxel with polymersomes |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1016/j.biomaterials.2016.07.023 |
Publisher version: | http://dx.doi.org/10.1016/j.biomaterials.2016.07.0... |
Language: | English |
Additional information: | Copyright © 2016 Elsevier Ltd. All rights reserved. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ |
Keywords: | Polymersomes; Tumor penetrating peptides; Peritoneal carcinomatosis; Paclitaxel; iRGD; NRP-1 |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry |
URI: | https://discovery.ucl.ac.uk/id/eprint/1508726 |
1. | China | 26 |
2. | United States | 5 |
3. | Korea, Republic of | 2 |
4. | Indonesia | 1 |
5. | Russian Federation | 1 |
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