{"id":2427,"date":"2019-07-08T08:54:15","date_gmt":"2019-07-08T07:54:15","guid":{"rendered":"https:\/\/ibb.uab.cat\/?p=2427"},"modified":"2019-07-08T10:50:52","modified_gmt":"2019-07-08T09:50:52","slug":"dr-a-villaverde-a-cxcr4-targeted-nanocarrier-achieves-highly-selective-tumor-uptake-in-diffuse-large-b-cell-lymphoma-mouse-models","status":"publish","type":"post","link":"https:\/\/ibb.uab.cat\/index.php\/2019\/07\/08\/dr-a-villaverde-a-cxcr4-targeted-nanocarrier-achieves-highly-selective-tumor-uptake-in-diffuse-large-b-cell-lymphoma-mouse-models\/","title":{"rendered":"Dr. A. Villaverde: A CXCR4-Targeted Nanocarrier Achieves Highly Selective Tumor Uptake In Diffuse Large B-Cell Lymphoma Mouse Models"},"content":{"rendered":"

http:\/\/www.haematologica.org\/content\/early\/2019\/06\/25\/haematol.2018.211490.article-info<\/span><\/h2>\n
A\u00efda<\/span>\u00a0Falg\u00e0s<\/span><\/span>,\u00a0Victor<\/span>\u00a0Pallar\u00e8s<\/span><\/span>,\u00a0Ugutz<\/span>\u00a0Unzueta<\/span><\/span>,\u00a0Mar\u00eda Virtudes<\/span>\u00a0C\u00e9spedes<\/span><\/span>,\u00a0Irene<\/span>\u00a0Arroyo-Solera<\/span><\/span>,\u00a0Mar\u00eda Jos\u00e9<\/span>\u00a0Moreno<\/span><\/span>,\u00a0Alberto<\/span>\u00a0Gallardo<\/span><\/span>,\u00a0Mar\u00eda Antonia<\/span>\u00a0Mangues<\/span><\/span>,\u00a0Jorge<\/span>\u00a0Sierra<\/span><\/span>,\u00a0Antonio<\/span>\u00a0Villaverde<\/span><\/span>,\u00a0Esther<\/span>\u00a0V\u00e1zquez<\/span><\/span>,\u00a0Ramon<\/span>\u00a0Mangues<\/span><\/span>,\u00a0Isolda<\/span>\u00a0Casanova<\/span><\/span><\/span><\/div>\n
Haematologica\u00a0<\/span>June 2019\u00a0<\/span>:\u00a0<\/span>haematol.2018.211490;\u00a0<\/span>Doi:<\/span>10.3324\/haematol.2018.211490<\/span><\/div>\n

Abstract<\/h2>\n

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 to specifically target 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 T22-DITOX-H6 administration, a nanoparticle incorporating a toxin with the same structure as the nanocarrier. Hence, the use of 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 without systemic toxicity.<\/p>\n","protected":false},"excerpt":{"rendered":"

http:\/\/www.haematologica.org\/content\/early\/2019\/06\/25\/haematol.2018.211490.article-info A\u00efda\u00a0Falg\u00e0s,\u00a0Victor\u00a0Pallar\u00e8s,\u00a0Ugutz\u00a0Unzueta,\u00a0Mar\u00eda Virtudes\u00a0C\u00e9spedes,\u00a0Irene\u00a0Arroyo-Solera,\u00a0Mar\u00eda Jos\u00e9\u00a0Moreno,\u00a0Alberto\u00a0Gallardo,\u00a0Mar\u00eda Antonia\u00a0Mangues,\u00a0Jorge\u00a0Sierra,\u00a0Antonio\u00a0Villaverde,\u00a0Esther\u00a0V\u00e1zquez,\u00a0Ramon\u00a0Mangues,\u00a0Isolda\u00a0Casanova Haematologica\u00a0June 2019\u00a0:\u00a0haematol.2018.211490;\u00a0Doi:10.3324\/haematol.2018.211490 Abstract 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 […]<\/p>\n","protected":false},"author":65,"featured_media":2429,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[4],"tags":[],"_links":{"self":[{"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/posts\/2427"}],"collection":[{"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/users\/65"}],"replies":[{"embeddable":true,"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/comments?post=2427"}],"version-history":[{"count":4,"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/posts\/2427\/revisions"}],"predecessor-version":[{"id":2436,"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/posts\/2427\/revisions\/2436"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/media\/2429"}],"wp:attachment":[{"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/media?parent=2427"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/categories?post=2427"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/tags?post=2427"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}