From 3D spheroids to tumor bearing mice: efficacy and distribution studies of trastuzumab-docetaxel immunoliposome in breast cancer
| Autor: | Sarah Giacometti, Bruno Lacarelle, Ariel Savina, Manon Carré, Bertrand Pourroy, Fanny Bouquet, Anne Rodallec, Guillaume Sicard, Raphaelle Fanciullino, Joseph Ciccolini |
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| Přispěvatelé: | Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2018 |
| Předmět: |
Biodistribution
[SDV]Life Sciences [q-bio] Biophysics Mice Nude Pharmaceutical Science Breast Neoplasms Bioengineering Docetaxel 02 engineering and technology Biomaterials Mice 03 medical and health sciences Drug Delivery Systems 0302 clinical medicine Breast cancer International Journal of Nanomedicine In vivo Trastuzumab Spheroids Cellular Antineoplastic Combined Chemotherapy Protocols Drug Discovery medicine Animals Humans Tissue Distribution skin and connective tissue diseases Cell Proliferation Chemistry Cell growth Organic Chemistry General Medicine 021001 nanoscience & nanotechnology medicine.disease In vitro 3. Good health 030220 oncology & carcinogenesis Liposomes Drug delivery Cancer research Female Erratum 0210 nano-technology medicine.drug |
| Zdroj: | International Journal of Nanomedicine International Journal of Nanomedicine, Dove Medical Press, 2018, 13, pp.6677-6688. ⟨10.2147/IJN.S179290⟩ International Journal of Nanomedicine, 2018, 13, pp.6677-6688. ⟨10.2147/IJN.S179290⟩ |
| ISSN: | 1178-2013 1176-9114 |
| DOI: | 10.2147/ijn.s179290 |
| Popis: | Anne Rodallec,1 Guillaume Sicard,1 Sarah Giacometti,1 Manon Carré,1 Bertrand Pourroy,2 Fanny Bouquet,3 Ariel Savina,3 Bruno Lacarelle,1 Joseph Ciccolini,1 Raphaelle Fanciullino1 1SMARTc Unit, Laboratory of Pharmacokinetics and Toxicology UFR Pharmacy, Center for Research on Cancer of Marseille, Inserm UMR1068, CNRS UMR7258, Aix Marseille University, Marseille, France; 2Pharmacy Department, APHM La Conception, Marseille, France; 3Roche Institute, Boulogne Billancourt, France Purpose: Nanoparticles are of rising interest in cancer research, but in vitro canonical cell monolayer models are not suitable to evaluate their efficacy when prototyping candidates. Here, we developed three-dimensional (3D) spheroid models to test the efficacy of trastuzumab-docetaxel immunoliposomes in breast cancer prior to further testing them in vivo. Materials and methods: Immunoliposomes were synthesized using the standard thin film method and maleimide linker. Two human breast cancer cell lines varying in Her2 expression were tested: Her2+ cells derived from metastatic site: mammary breast MDA-MB-453 and triple-negative MDA-MB-231 cells. 3D spheroids were developed and tested with fluorescence detection to evaluate viability. In vivo efficacy and biodistribution studies were performed on xenograft bearing nude mice using fluorescent and bioluminescent imaging. Results: In vitro, antiproliferative efficacy was dependent upon cell type, size of the spheroids, and treatment scheduling, resulting in subsequent changes between tested conditions and invivo results. Immunoliposomes performed better than free docetaxel + free trastuzumab and ado-trastuzumab emtansine (T-DM1). On MDA-MB-453 and MDA-MB-231 cell growth was reduced by 76% and 25%, when compared to free docetaxel + free trastuzumab and by 85% and 70% when compared to T-DM1, respectively. In vivo studies showed tumor accumulation ranging from 3% up to 15% of the total administered dose in MDA-MB-453 and MDA-MB-231 bearing mice. When compared to free docetaxel + free trastuzumab, tumor growth was reduced by 89% (MDA-MB-453) and 25% (MDA-MB-231) and reduced by 66% (MDA-MB-453) and 29% (MDA-MB-231) when compared to T-DM1, an observation in line with data collected from 3D spheroids experiments. Conclusion: We demonstrated the predictivity of 3D in vitro models when developing and testing nanoparticles in experimental oncology. In vitro and in vivo data showed efficient drug delivery with higher efficacy and prolonged survival with immunoliposomes when compared to current anti-Her2 breast cancer strategies. Keywords: docetaxel, trastuzumab, breast cancer, immunoliposome, spheroids, distribution, tumor xenograftErratumfor this paper has been published |
| Databáze: | OpenAIRE |
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