title: Passive versus active tumor targeting using RGD- and NGR-modified polymeric nanomedicines.
abstract: 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.
authors.affiliation: Department of Experimental Molecular Imaging, University Hospital and Helmholtz Institute for Biomedical Engineering, RWTH Aachen , Pauwelsstrasse 30, 52074 Aachen, Germany.
authors.forename: Sijumon
authors.initials: S
authors.lastname: Kunjachan
authors.forename: Robert
authors.initials: R
authors.lastname: Pola
authors.forename: Felix
authors.initials: F
authors.lastname: Gremse
authors.forename: Benjamin
authors.initials: B
authors.lastname: Theek
authors.forename: Josef
authors.initials: J
authors.lastname: Ehling
authors.forename: Diana
authors.initials: D
authors.lastname: Moeckel
authors.forename: Benita
authors.initials: B
authors.lastname: Hermanns-Sachweh
authors.forename: Michal
authors.initials: M
authors.lastname: Pechar
authors.forename: Karel
authors.initials: K
authors.lastname: Ulbrich
authors.forename: Wim E
authors.initials: WE
authors.lastname: Hennink
authors.forename: Gert
authors.initials: G
authors.lastname: Storm
authors.forename: Wiltrud
authors.initials: W
authors.lastname: Lederle
authors.forename: Fabian
authors.initials: F
authors.lastname: Kiessling
authors.forename: Twan
authors.initials: T
authors.lastname: Lammers
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D004058:Diffusion; D006801:Humans; D051379:Mice; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D053761:Nanocomposites / Q000737:chemistry / Q000648:ultrastructure; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D009842:Oligopeptides / Q000737:chemistry / Q000493:pharmacokinetics*; D010316:Particle Size
chemical_list: D000970:Antineoplastic Agents; C526428:NGR peptide; D053769:Nanocapsules; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid