Monitoring EPR Effect Dynamics during Nanotaxane Treatment with Theranostic Polymeric Micelles

Ilaria Biancacci; Federica De Lorenzi; Benjamin Theek; Xiangyang Bai; Jan Niklas May; Lorena Consolino; Maike Baues; Diana Moeckel; Felix Gremse; Saskia von Stillfried; Asmaa El Shafei; Karina Benderski; Armin Azadkhah Shalmani; Alec Wang; Jeffrey Momoh; Quim Peña; Eva Miriam Buhl; Johannes Buyel; Wim Hennink; Fabian Kiessling; Josbert Metselaar; Yang Shi; Twan Lammers

doi:10.1002/advs.202103745

Monitoring EPR Effect Dynamics during Nanotaxane Treatment with Theranostic Polymeric Micelles

Ilaria Biancacci
, Federica De Lorenzi
, Benjamin Theek
, Xiangyang Bai
, Jan Niklas May
, Lorena Consolino
, Maike Baues
, Diana Moeckel
, Felix Gremse
, Saskia von Stillfried
, Asmaa El Shafei
, Karina Benderski
, Armin Azadkhah Shalmani
, Alec Wang
, Jeffrey Momoh
, Quim Peña
, Eva Miriam Buhl
, Johannes Buyel
, Wim Hennink
, Fabian Kiessling

Josbert Metselaar, Yang Shi^*, Twan Lammers^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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 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.

Original language	English
Article number	2103745
Pages (from-to)	1-9
Journal	Advanced Science
Volume	9
Issue number	10
DOIs	https://doi.org/10.1002/advs.202103745
Publication status	Published - 5 Apr 2022

Bibliographical 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.

Funding

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. 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.

Keywords

cancer nanomedicine
EPR effect
polymeric micelles
theranostics
tumor targeting

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Advanced Science - 2022 - Biancacci - Monitoring EPR Effect Dynamics during Nanotaxane Treatment with Theranostic PolymericFinal published version, 2.11 MBLicence: CC BY

Cite this

Biancacci, I., De Lorenzi, F., Theek, B., Bai, X., May, J. N., Consolino, L., Baues, M., Moeckel, D., Gremse, F., von Stillfried, S., El Shafei, A., Benderski, K., Azadkhah Shalmani, A., Wang, A., Momoh, J., Peña, Q., Buhl, E. M., Buyel, J., Hennink, W., ... Lammers, T. (2022). Monitoring EPR Effect Dynamics during Nanotaxane Treatment with Theranostic Polymeric Micelles. Advanced Science, 9(10), 1-9. Article 2103745. https://doi.org/10.1002/advs.202103745

@article{e4ecd70494dc4c0dafe06974c4039607,

title = "Monitoring EPR Effect Dynamics during Nanotaxane Treatment with Theranostic Polymeric Micelles",

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 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.",

keywords = "cancer nanomedicine, EPR effect, polymeric micelles, theranostics, tumor targeting",

author = "Ilaria Biancacci and \{De Lorenzi\}, Federica and Benjamin Theek and Xiangyang Bai and May, \{Jan Niklas\} and Lorena Consolino and Maike Baues and Diana Moeckel and Felix Gremse and \{von Stillfried\}, Saskia and \{El Shafei\}, Asmaa and Karina Benderski and \{Azadkhah Shalmani\}, Armin and Alec Wang and Jeffrey Momoh and Quim Pe{\~n}a and Buhl, \{Eva Miriam\} and Johannes Buyel and Wim Hennink and Fabian Kiessling and Josbert Metselaar and Yang Shi and Twan Lammers",

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: {\textcopyright} 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.",

year = "2022",

month = apr,

day = "5",

doi = "10.1002/advs.202103745",

language = "English",

volume = "9",

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Biancacci, I, De Lorenzi, F, Theek, B, Bai, X, May, JN, Consolino, L, Baues, M, Moeckel, D, Gremse, F, von Stillfried, S, El Shafei, A, Benderski, K, Azadkhah Shalmani, A, Wang, A, Momoh, J, Peña, Q, Buhl, EM, Buyel, J, Hennink, W, Kiessling, F, Metselaar, J, Shi, Y & Lammers, T 2022, 'Monitoring EPR Effect Dynamics during Nanotaxane Treatment with Theranostic Polymeric Micelles', Advanced Science, vol. 9, no. 10, 2103745, pp. 1-9. https://doi.org/10.1002/advs.202103745

TY - JOUR

T1 - Monitoring EPR Effect Dynamics during Nanotaxane Treatment with Theranostic Polymeric Micelles

AU - Biancacci, Ilaria

AU - De Lorenzi, Federica

AU - Theek, Benjamin

AU - Bai, Xiangyang

AU - May, Jan Niklas

AU - Consolino, Lorena

AU - Baues, Maike

AU - Moeckel, Diana

AU - Gremse, Felix

AU - von Stillfried, Saskia

AU - El Shafei, Asmaa

AU - Benderski, Karina

AU - Azadkhah Shalmani, Armin

AU - Wang, Alec

AU - Momoh, Jeffrey

AU - Peña, Quim

AU - Buhl, Eva Miriam

AU - Buyel, Johannes

AU - Hennink, Wim

AU - Kiessling, Fabian

AU - Metselaar, Josbert

AU - Shi, Yang

AU - Lammers, Twan

N1 - 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.

PY - 2022/4/5

Y1 - 2022/4/5

N2 - 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 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.

AB - 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 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.

KW - cancer nanomedicine

KW - EPR effect

KW - polymeric micelles

KW - theranostics

KW - tumor targeting

UR - https://www.scopus.com/pages/publications/85123579288

U2 - 10.1002/advs.202103745

DO - 10.1002/advs.202103745

M3 - Article

AN - SCOPUS:85123579288

SN - 2198-3844

VL - 9

SP - 1

EP - 9

JO - Advanced Science

JF - Advanced Science

IS - 10

M1 - 2103745

ER -

Monitoring EPR Effect Dynamics during Nanotaxane Treatment with Theranostic Polymeric Micelles

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

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