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Open AccessArticle

Trastuzumab-Targeted Biodegradable Nanoparticles for Enhanced Delivery of Dasatinib in HER2+ Metastasic Breast Cancer

1
Dpto. Inorgánica, Orgánica y Bioquímica, Facultad de Farmacia de Albacete, UCLM, 02071 Albacete, Spain
2
Oncología Traslacional, Unidad de Investigación del Complejo Hospitalario Universitario de Albacete, 02071 Albacete, Spain
3
Centro Regional de Investigaciones Biomédicas (CRIB), UCLM, 02008 Albacete, Spain
4
Dpto. Química Física, Facultad de Farmacia de Albacete, UCLM, 02071 Albacete, Spain
5
Instituto de Energías Renovables, UCLM, 02071 Albacete, Spain
6
Dpto. Inorgánica, Orgánica y Bioquímica, Facultad de Ciencias y Tecnologías Químicas de Ciudad Real, UCLM, 13075 Ciudad Real, Spain
7
Experimental Therapeutics Unit, Hospital clínico San Carlos, IdISSC and CIBERONC, 28029 Madrid, Spain
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Nanomaterials 2019, 9(12), 1793; https://doi.org/10.3390/nano9121793
Received: 22 November 2019 / Revised: 12 December 2019 / Accepted: 13 December 2019 / Published: 16 December 2019
Dasatinib (DAS) is a multikinase inhibitor that acts on several signaling kinases. DAS is used as a second-line treatment for chronic accelerated myeloid and Philadelphia chromosome-positive acute lymphoblastic leukemia. The therapeutic potential of DAS in other solid tumours is under evaluation. As for many other compounds, an improvement in their pharmacokinetic and delivery properties would potential augment the efficacy. Antibody-targeted biodegradable nanoparticles can be useful in targeted cancer therapy. DAS has shown activity in human epidermal growth factor receptor 2 (HER2) positive tumors, so conjugation of this compound with the anti-HER2 antibody trastuzumab (TAB) with the use of nanocarriers could improve its efficacy. TAB-targeted DAS-loaded nanoparticles were generated by nanotechnology. The guided nanocarriers enhanced in vitro cytotoxicity of DAS against HER2 human breast cancer cell lines. Cellular mechanistic, release studies and nanoparticles stability were undertaken to provide evidences for positioning DAS-loaded TAB-targeted nanoparticles as a potential strategy for further development in HER2-overexpressing breast cancer therapy. View Full-Text
Keywords: Dasatinib; trastuzumab; HER metastasic breast cancer; antibody-targeted nanoparticles Dasatinib; trastuzumab; HER metastasic breast cancer; antibody-targeted nanoparticles
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MDPI and ACS Style

Niza, E.; Noblejas-López, M.M.; Bravo, I.; Nieto-Jiménez, C.; Castro-Osma, J.A.; Canales-Vázquez, J.; Lara-Sanchez, A.; Galán Moya, E.M.; Burgos, M.; Ocaña, A.; Alonso-Moreno, C. Trastuzumab-Targeted Biodegradable Nanoparticles for Enhanced Delivery of Dasatinib in HER2+ Metastasic Breast Cancer. Nanomaterials 2019, 9, 1793.

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