Monitoring EPR Effect Dynamics during Nanotaxane Treatment with Theranostic Polymeric Micelles
Biancacci, Ilaria; De Lorenzi, Federica; Theek, Benjamin; Bai, Xiangyang; May, Jan Niklas; Consolino, Lorena; Baues, Maike; Moeckel, Diana; Gremse, Felix; von Stillfried, Saskia; El Shafei, Asmaa; Benderski, Karina; Azadkhah Shalmani, Armin; Wang, Alec; Momoh, Jeffrey; Peña, Quim; Buhl, Eva Miriam; Buyel, Johannes; Hennink, Wim; Kiessling, Fabian; Metselaar, Josbert; Shi, Yang; Lammers, Twan
(2022) Advanced Science, volume 9, issue 10, pp. 1 - 9
(Article)
Abstract
Cancer nanomedicines rely on the enhanced permeability and retention (EPR) effect for efficient target site accumulation. The EPR effect, however, is highly heterogeneous among different tumor types and cancer patients and its extent is expected to dynamically change during the course of nanochemotherapy. Here the authors set out to longitudinally
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study the dynamics of the EPR effect upon single- and double-dose nanotherapy with fluorophore-labeled and paclitaxel-loaded polymeric micelles. Using computed tomography-fluorescence molecular tomography imaging, it is shown that the extent of nanomedicine tumor accumulation is predictive for therapy outcome. It is also shown that the interindividual heterogeneity in EPR-based tumor accumulation significantly increases during treatment, especially for more efficient double-dose nanotaxane therapy. Furthermore, for double-dose micelle therapy, tumor accumulation significantly increased over time, from 7% injected dose per gram (ID g–1) upon the first administration to 15% ID g–1 upon the fifth administration, contributing to more efficient inhibition of tumor growth. These findings shed light on the dynamics of the EPR effect during nanomedicine treatment and they exemplify the importance of using imaging in nanomedicine treatment prediction and clinical translation.
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Keywords: cancer nanomedicine, EPR effect, polymeric micelles, theranostics, tumor targeting, Medicine (miscellaneous), General Chemical Engineering, General Materials Science, Biochemistry, Genetics and Molecular Biology (miscellaneous), General Engineering, General Physics and Astronomy
ISSN: 2198-3844
Publisher: Wiley-VCH Verlag
Note: Funding Information: I.B., F.D.L., and B.T. contributed equally to this work. The authors gratefully acknowledge financial support by the German Research Foundation (DFG: GRK 2375 (Project No. 331065168)), SFB 1382 (Project No. 403224013), SFB 1066, LA2937/4-1, SH1223/1-1), the German Federal Ministry of Research and Education (BMBF: Gezielter Wirkstofftransport, PP-TNBC, Project No. 16GW0319K), the European Union (European Fund for Regional Development: TAKTIRA; Project No. EFRE-0801767), and the European Research Council (ERC Consolidator grant; Meta-Targeting; Project No. 864121). This work was actively supported by the Core Facility “Two-Photon Imaging”, a Core Facility of the Interdisciplinary Center for Clinical Research (IZKF) Aachen within the Faculty of Medicine at RWTH Aachen University. Open Access funding enabled and organized by Projekt DEAL. Funding Information: I.B., F.D.L., and B.T. contributed equally to this work. The authors gratefully acknowledge financial support by the German Research Foundation (DFG: GRK 2375 (Project No. 331065168)), SFB 1382 (Project No. 403224013), SFB 1066, LA2937/4‐1, SH1223/1‐1), the German Federal Ministry of Research and Education (BMBF: Gezielter Wirkstofftransport, PP‐TNBC, Project No. 16GW0319K), the European Union (European Fund for Regional Development: TAKTIRA; Project No. EFRE‐0801767), and the European Research Council (ERC Consolidator grant; Meta‐Targeting; Project No. 864121). This work was actively supported by the Core Facility “Two‐Photon Imaging”, a Core Facility of the Interdisciplinary Center for Clinical Research (IZKF) Aachen within the Faculty of Medicine at RWTH Aachen University. Publisher Copyright: © 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.
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