A CXCR4-targeted nanocarrier achieves highly selective tumor uptake in diffuse large B-cell lymphoma mouse models
| Autor: | Falgàs, Aïda, Pallarès i Goitiz, Irantzu, Unzueta Elorza, Ugutz, Céspedes, María Virtudes, Arroyo-Solera, Irene, Moreno, María José, Sierra, Jorge, Gallardo, Alberto, Mangues, Ma Antonia, Villaverde Corrales, Antonio, Vázquez Gómez, Esther, Mangues, Ramon, Casanova Rigat, Isolda, Universitat Autònoma de Barcelona |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Receptors
CXCR4 Vincristine Non-Hodgkin Lymphoma Antineoplastic Agents Article Mice 03 medical and health sciences 0302 clinical medicine Antineoplastic Combined Chemotherapy Protocols medicine Animals Humans Tissue Distribution Doxorubicin Cyclophosphamide CXCR4 antagonist Chemistry Hematology medicine.disease Lymphoma Cancer cell Cancer research Prednisone Rituximab Lymphoma Large B-Cell Diffuse Neoplasm Recurrence Local Nanocarriers Diffuse large B-cell lymphoma Signal Transduction 030215 immunology medicine.drug |
| Zdroj: | Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona HAEMATOLOGICA r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau instname Haematologica |
| ISSN: | 0390-6078 |
| Popis: | Altres ajuts: U COST Action CA 17140 to RM; FIS PI17/01246, RD12/0036/0071 and FIS PI14/00450 to JS; CP15/00163 to MVC; FIS PI15/00272 to EV ; CIBER-BBN [CB06/01/1031 and 4NanoMets to RM ; and VENOM4CANCER to AV. Grant from La Generalitat de Catalunya (PERIS) [SLT002/16/00433 to JS One-third of diffuse large B-cell lymphoma patients are refractory to initial treatment or relapse after rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone chemotherapy. In these patients, CXCR4 overexpression (CXCR4+) associates with lower overall and disease-free survival. Nanomedicine pursues active targeting to selectively deliver antitumor agents to cancer cells; a novel approach that promises to revolutionize therapy by dramatically increasing drug concentration in target tumor cells. In this study, we intravenously administered a liganded protein nanocarrier (T22-GFP-H6) targeting CXCR4+ lymphoma cells in mouse models to assess its selectivity as a nanocarrier by measuring its tissue biodistribution in cancer and normal cells. No previous protein-based nanocarrier has been described as specifically targeting lymphoma cells. T22-GFP-H6 achieved a highly selective tumor uptake in a CXCR4+ lymphoma subcutaneous model, as detected by fluorescent emission. We demonstrated that tumor uptake was CXCR4-dependent because pretreatment with AMD3100, a CXCR4 antagonist, significantly reduced tumor uptake. Moreover, in contrast to CXCR4+ subcutaneous models, CXCR4- tumors did not accumulate the nanocarrier. Most importantly, after intravenous injection in a disseminated model, the nanocarrier accumulated and internalized in all clinically relevant organs affected by lymphoma cells with negligible distribution to unaffected tissues. Finally, we obtained antitumor effect without toxicity in a CXCR4+ lymphoma model by administration of T22-DITOX-H6, a nanoparticle incorporating a toxin with the same structure as the nanocarrier. Hence, the use of the T22-GFP-H6 nanocarrier could be a good strategy to load and deliver drugs or toxins to treat specifically CXCR4-mediated refractory or relapsed diffuse large B-cell lymphoma |
| Databáze: | OpenAIRE |
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