Monitoring EPR Effect Dynamics during Nanotaxane Treatment with Theranostic Polymeric Micelles

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 nanochemoth...

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Published in:	Advanced science 2022-04, Vol.9 (10), p.e2103745-n/a
Main Authors:	Biancacci, Ilaria, De Lorenzi, Federica, Theek, Benjamin, Bai, Xiangyang, May, Jan‐Niklas, Consolino, Lorena, Baues, Maike, Moeckel, Diana, Gremse, Felix, 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
Format:	Article
Language:	eng
Subjects:	cancer nanomedicine Drug delivery systems Drug dosages EPR effect Humans Localization Metastasis Micelles Nanomedicine Nanoparticles Permeability polymeric micelles Theranostic Nanomedicine - methods theranostics Tomography tumor targeting Tumors Variance analysis
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Summary:	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. Using fluorophore‐labeled and paclitaxel‐loaded polymeric micelles, the authors demonstrate that: 1) the interindividual heterogeneity in nanomedicine tumor accumulation increases during the course of treatment; 2) the extent of nanomedicine tumor accumulation is predictive for therapy outcome; and 3) imaging tumor accumulation multiple times during treatment more favorably predicts therapy outcome than imaging just once at the start of therapy.
ISSN:	2198-3844 2198-3844