Nanoliposome targeting in breast cancer is influenced by the tumor microenvironment
| Autor: | Elena Geretti, Samantha Merrigan, Nancy Dumont, Jason Turpin, Cynthia Lavoie, Christopher W. Espelin, Daryl C. Drummond, Lia Luus, Vasilios Papavasiliou, G. Gary Sahagian, Thomas Wickham, Bart S. Hendriks, Omid Ghasemi, Walid S. Kamoun, William J. Muller |
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| Rok vydání: | 2018 |
| Předmět: |
Immunoconjugates
Receptor ErbB-2 Biomedical Engineering Pharmaceutical Science Medicine (miscellaneous) Bioengineering Breast Neoplasms 02 engineering and technology Metastasis Polyethylene Glycols 03 medical and health sciences Mice Breast cancer Drug Delivery Systems Cell Line Tumor medicine Lymphatic vessel Tumor Microenvironment Animals General Materials Science Doxorubicin 030304 developmental biology 0303 health sciences Tumor microenvironment Liposome Antibiotics Antineoplastic business.industry 021001 nanoscience & nanotechnology medicine.disease medicine.anatomical_structure Liposomes Cancer research Disease Progression Molecular Medicine Immunohistochemistry Female 0210 nano-technology business Ex vivo medicine.drug Single-Chain Antibodies |
| Zdroj: | Nanomedicine : nanotechnology, biology, and medicine. 17 |
| ISSN: | 1549-9642 |
| Popis: | MM-302 is an anti-HER2 antibody-targeted pegylated liposomal doxorubicin designed to deliver doxorubicin specifically to HER2-expressing solid tumors. The delivery and activity of MM-302 were evaluated in orthotopic, transgenic, and intravenous breast cancer models expressing varying levels of HER2 that metastasize to some of the most common sites of dissemination for breast cancer, namely, lung, liver, and brain. Metastatic burden was quantified by gross evaluation, immunohistochemistry (IHC), and bioluminescent imaging. Liposome delivery was quantified by IHC and ex vivo fluorescent imaging. Unlike its non-targeted counterpart, pegylated liposomal doxorubicin (PLD), MM-302 showed activity at controlling both primary and metastatic tumor burden in all models tested. The effect of HER2-targeting was greatest in the lung where lymphatic vessel density and MM-302 delivery were highest. Our data indicate that the therapeutic advantage of actively targeting a nanoliposome with an antibody is influenced by both target expression and the tumor microenvironment. |
| Databáze: | OpenAIRE |
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