Passive versus active tumor targeting using RGD- and NGR-modified polymeric nanomedicines

0425232 - ÚMCH 2014 RIV US eng J - Journal Article
Kunjachan, S. - Pola, Robert - Gremse, F. - Theek, B. - Ehling, J. - Moeckel, D. - Hermanns-Sachweh, B. - Pechar, Michal - Ulbrich, Karel - Hennink, W. E. - Storm, G. - Lederle, W. - Kiessling, F. - Lammers, T.
Passive versus active tumor targeting using RGD- and NGR-modified polymeric nanomedicines.
Nano Letters. Roč. 14, č. 2 (2014), s. 972-981. ISSN 1530-6984. E-ISSN 1530-6992
R&D Projects: GA ČR GCP207/12/J030
Institutional support: RVO:61389013
Keywords : nanomedicine * drug targeting * EPR
Subject RIV: CD - Macromolecular Chemistry
Impact factor: 13.592, year: 2014

Enhanced permeability and retention (EPR) and the (over-) expression of angiogenesis-related surface receptors are key features of tumor blood vessels. As a consequence, EPR-mediated passive and Arg-Gly-Asp (RGD) and Asn-Gly-Arg (NGR) based active tumor targeting have received considerable attention in the last couple of years. Using several different in vivo and ex vivo optical imaging techniques, we here visualized and quantified the benefit of RGD- and NGR-based vascular vs EPR-mediated passive tumor targeting. This was done using 10 nm sized polymeric nanocarriers, which were either labeled with DY-676 (peptide-modified polymers) or with DY-750 (peptide-free polymers). Upon coinjection into mice bearing both highly leaky CT26 and poorly leaky BxPC3 tumors, it was found that vascular targeting did work, resulting in rapid and efficient early binding to tumor blood vessels, but that over time, passive targeting was significantly more efficient, leading to higher overall levels and to more efficient retention within tumors. Although this situation might be different for larger carrier materials, these insights indicate that caution should be taken not to overestimate the potential of active over passive tumor targeting.
Permanent Link: http://hdl.handle.net/11104/0231626