Analysis of nanomedicine primary tumor vs. metastasis targeting using clinical-stage core-crosslinked polymeric micelles
Summary: Targeting and treating metastatic cancer remain major clinical challenges. We developed an optically imageable metastatic mouse model based on near-infrared protein-expressing 4T1 triple-negative breast cancer cells. Using multimodal imaging, we studied the tumor and metastasis tropism of c...
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Elsevier
2025-08-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725008575 |
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| author | Larissa Yokota Rizzo Federica De Lorenzi Saskia von Stillfried Seyed Mohammadali Dadfar Qizhi Hu Sanjay Tiwari Claus-Christian Glüer Marielle Thewissen Felix Gremse Stephan Rütten Peter Boor Wilhelm Jahnen-Dechent Ruth Knüchel-Clarke Fabian Kiessling Cristianne J.F. Rijcken Alexandros Marios Sofias Twan Lammers |
| author_facet | Larissa Yokota Rizzo Federica De Lorenzi Saskia von Stillfried Seyed Mohammadali Dadfar Qizhi Hu Sanjay Tiwari Claus-Christian Glüer Marielle Thewissen Felix Gremse Stephan Rütten Peter Boor Wilhelm Jahnen-Dechent Ruth Knüchel-Clarke Fabian Kiessling Cristianne J.F. Rijcken Alexandros Marios Sofias Twan Lammers |
| author_sort | Larissa Yokota Rizzo |
| collection | DOAJ |
| description | Summary: Targeting and treating metastatic cancer remain major clinical challenges. We developed an optically imageable metastatic mouse model based on near-infrared protein-expressing 4T1 triple-negative breast cancer cells. Using multimodal imaging, we studied the tumor and metastasis tropism of core-crosslinked polymeric micelles (CCPMs) as well as the antitumor and antimetastatic efficacy of clinical-stage docetaxel-loaded CCPMs (docetaxel-CCPMs). We show that nanomedicines effectively target metastases, albeit with lower efficiency than primary tumors. Tumor microenvironment analysis revealed that metastases are more vascularized than primary tumors but also present with higher levels of collagen crosslinking, thereby hindering nanomedicine accumulation. A comparison of mouse and human tumors and metastases showed similarities and differences, consistently demonstrating increased vascularization in metastases. In mice, docetaxel-CCPMs outperformed standard docetaxel in terms of efficacy and toxicity. These findings underscore the potential of nanomedicine to improve metastatic cancer therapy, and they offer new insights into the tumor and metastasis microenvironment as a determinant of targeted drug delivery. |
| format | Article |
| id | doaj-art-6b2e3b158b224d4c802fa96f44ad5c42 |
| institution | DOAJ |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-6b2e3b158b224d4c802fa96f44ad5c422025-08-20T03:02:44ZengElsevierCell Reports2211-12472025-08-0144811608610.1016/j.celrep.2025.116086Analysis of nanomedicine primary tumor vs. metastasis targeting using clinical-stage core-crosslinked polymeric micellesLarissa Yokota Rizzo0Federica De Lorenzi1Saskia von Stillfried2Seyed Mohammadali Dadfar3Qizhi Hu4Sanjay Tiwari5Claus-Christian Glüer6Marielle Thewissen7Felix Gremse8Stephan Rütten9Peter Boor10Wilhelm Jahnen-Dechent11Ruth Knüchel-Clarke12Fabian Kiessling13Cristianne J.F. Rijcken14Alexandros Marios Sofias15Twan Lammers16Department of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging (ExMI), RWTH Aachen University Hospital, Aachen, North Rhine-Westphalia (NRW) 52074, GermanyDepartment of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging (ExMI), RWTH Aachen University Hospital, Aachen, North Rhine-Westphalia (NRW) 52074, Germany; Center for Integrated Oncology Aachen (CIOA), RWTH Aachen University Hospital, Aachen, North Rhine-Westphalia (NRW) 52074, Germany; Department of Medical Biosciences, Radboud University Medical Centre, Nijmegen, Gelderland 6525 GA, the NetherlandsCenter for Integrated Oncology Aachen (CIOA), RWTH Aachen University Hospital, Aachen, North Rhine-Westphalia (NRW) 52074, Germany; Institute of Pathology, RWTH Aachen University Hospital, Aachen, North Rhine-Westphalia (NRW) 52074, GermanyDepartment of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging (ExMI), RWTH Aachen University Hospital, Aachen, North Rhine-Westphalia (NRW) 52074, GermanyCristal Therapeutics, Maastricht, Limburg 6229 GT, the NetherlandsDepartment of Radiology and Neuroradiology, Section Biomedical Imaging, Molecular Imaging North Competence Center (MOIN CC), University Hospital Schleswig-Holstein, 24105 Kiel, Schleswig-Holstein, GermanyDepartment of Radiology and Neuroradiology, Section Biomedical Imaging, Molecular Imaging North Competence Center (MOIN CC), University Hospital Schleswig-Holstein, 24105 Kiel, Schleswig-Holstein, GermanyCristal Therapeutics, Maastricht, Limburg 6229 GT, the NetherlandsDepartment of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging (ExMI), RWTH Aachen University Hospital, Aachen, North Rhine-Westphalia (NRW) 52074, GermanyInstitute of Pathology, RWTH Aachen University Hospital, Aachen, North Rhine-Westphalia (NRW) 52074, Germany; Electron Microscopy Facility, RWTH Aachen University Hospital, Aachen, North Rhine-Westphalia (NRW) 52074, GermanyCenter for Integrated Oncology Aachen (CIOA), RWTH Aachen University Hospital, Aachen, North Rhine-Westphalia (NRW) 52074, Germany; Institute of Pathology, RWTH Aachen University Hospital, Aachen, North Rhine-Westphalia (NRW) 52074, GermanyHelmholtz Institute for Biomedical Technology, RWTH Aachen, Aachen, North Rhine-Westphalia (NRW) 52074, GermanyCenter for Integrated Oncology Aachen (CIOA), RWTH Aachen University Hospital, Aachen, North Rhine-Westphalia (NRW) 52074, Germany; Institute of Pathology, RWTH Aachen University Hospital, Aachen, North Rhine-Westphalia (NRW) 52074, GermanyInstitute for Experimental Molecular Imaging (ExMI), RWTH Aachen University Hospital, Aachen, North Rhine-Westphalia (NRW) 52074, Germany; Fraunhofer Institute for Digital Medicine MEVIS, 28359 Bremen, GermanyCristal Therapeutics, Maastricht, Limburg 6229 GT, the NetherlandsDepartment of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging (ExMI), RWTH Aachen University Hospital, Aachen, North Rhine-Westphalia (NRW) 52074, Germany; Center for Integrated Oncology Aachen (CIOA), RWTH Aachen University Hospital, Aachen, North Rhine-Westphalia (NRW) 52074, GermanyDepartment of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging (ExMI), RWTH Aachen University Hospital, Aachen, North Rhine-Westphalia (NRW) 52074, Germany; Center for Integrated Oncology Aachen (CIOA), RWTH Aachen University Hospital, Aachen, North Rhine-Westphalia (NRW) 52074, Germany; Corresponding authorSummary: Targeting and treating metastatic cancer remain major clinical challenges. We developed an optically imageable metastatic mouse model based on near-infrared protein-expressing 4T1 triple-negative breast cancer cells. Using multimodal imaging, we studied the tumor and metastasis tropism of core-crosslinked polymeric micelles (CCPMs) as well as the antitumor and antimetastatic efficacy of clinical-stage docetaxel-loaded CCPMs (docetaxel-CCPMs). We show that nanomedicines effectively target metastases, albeit with lower efficiency than primary tumors. Tumor microenvironment analysis revealed that metastases are more vascularized than primary tumors but also present with higher levels of collagen crosslinking, thereby hindering nanomedicine accumulation. A comparison of mouse and human tumors and metastases showed similarities and differences, consistently demonstrating increased vascularization in metastases. In mice, docetaxel-CCPMs outperformed standard docetaxel in terms of efficacy and toxicity. These findings underscore the potential of nanomedicine to improve metastatic cancer therapy, and they offer new insights into the tumor and metastasis microenvironment as a determinant of targeted drug delivery.http://www.sciencedirect.com/science/article/pii/S2211124725008575CP: Cancer |
| spellingShingle | Larissa Yokota Rizzo Federica De Lorenzi Saskia von Stillfried Seyed Mohammadali Dadfar Qizhi Hu Sanjay Tiwari Claus-Christian Glüer Marielle Thewissen Felix Gremse Stephan Rütten Peter Boor Wilhelm Jahnen-Dechent Ruth Knüchel-Clarke Fabian Kiessling Cristianne J.F. Rijcken Alexandros Marios Sofias Twan Lammers Analysis of nanomedicine primary tumor vs. metastasis targeting using clinical-stage core-crosslinked polymeric micelles Cell Reports CP: Cancer |
| title | Analysis of nanomedicine primary tumor vs. metastasis targeting using clinical-stage core-crosslinked polymeric micelles |
| title_full | Analysis of nanomedicine primary tumor vs. metastasis targeting using clinical-stage core-crosslinked polymeric micelles |
| title_fullStr | Analysis of nanomedicine primary tumor vs. metastasis targeting using clinical-stage core-crosslinked polymeric micelles |
| title_full_unstemmed | Analysis of nanomedicine primary tumor vs. metastasis targeting using clinical-stage core-crosslinked polymeric micelles |
| title_short | Analysis of nanomedicine primary tumor vs. metastasis targeting using clinical-stage core-crosslinked polymeric micelles |
| title_sort | analysis of nanomedicine primary tumor vs metastasis targeting using clinical stage core crosslinked polymeric micelles |
| topic | CP: Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725008575 |
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