Targeted drug distribution in tumor extracellular fluid of GD2-expressing neuroblastoma patient-derived xenografts using SN-38-loaded nanoparticles conjugated to the monoclonal antibody 3F8
Por:
Monterrubio C, Paco-Mercader S, Gene-Olaciregui N, Pascual-Pastó G, Vilà-Ubach M, Cuadrado-Vilanova M, Ferrandiz MM, Castillo-Ecija H, Glisoni R, Kuplennik N, Jungbluth A, de Torres C, Lavarino C, Cheung NV, Mora J, Sosnik A and Carcaboso AM
Publicada:
10 ene 2017
Ahead of Print:
12 abr 2017
Categoría:
Pharmaceutical science
Resumen:
Neuroblastoma is a pediatric solid tumor with high expression of the tumor associated antigen disialoganglioside GD2. Despite initial response to induction therapy, nearly 50% of high-risk neuroblastomas recur because of chemoresistance. Here we encapsulated the topoisomerase-I inhibitor SN-38 in polymeric nanoparticles (NPs) surface-decorated with the anti-GD2 mouse mAb 3F8 at a mean density of seven antibody molecules per NP. The accumulation of drug-loaded NPs targeted with 3F8 versus with control antibody was monitored by microdialysis in patient-derived GD2-expressing neuroblastoma xenografts. We showed that the extent of tumor penetration by SN-38 was significantly higher in mice receiving the targeted nano-drug delivery system when compared to non-targeted system or free drug. This selective penetration of the tumor extracellular fluid translated into a strong anti-tumor effect prolonging survival of mice bearing GD2-high neuroblastomas in vivo.
Filiaciones:
Monterrubio C:
Institut de Recerca Sant Joan de Déu, 08950 Barcelona, Spain
Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Deu, 08950 Barcelona, Spain
Paco-Mercader S:
Institut de Recerca Sant Joan de Déu, 08950 Barcelona, Spain
Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Deu, 08950 Barcelona, Spain
Pascual-Pastó G:
Institut de Recerca Sant Joan de Déu, 08950 Barcelona, Spain
Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Deu, 08950 Barcelona, Spain
Vilà-Ubach M:
Institut de Recerca Sant Joan de Déu, 08950 Barcelona, Spain
Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Deu, 08950 Barcelona, Spain
Cuadrado-Vilanova M:
Institut de Recerca Sant Joan de Déu, 08950 Barcelona, Spain
Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Deu, 08950 Barcelona, Spain
Ferrandiz MM:
Institut de Recerca Sant Joan de Déu, 08950 Barcelona, Spain
Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Deu, 08950 Barcelona, Spain
Castillo-Ecija H:
Institut de Recerca Sant Joan de Déu, 08950 Barcelona, Spain
Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Deu, 08950 Barcelona, Spain
Glisoni R:
CONICET-Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, Universidad de Buenos Aires, CP1113 Buenos Aires, Argentina
Kuplennik N:
Laboratory of Pharmaceutical Nanomaterials Science, Department of Materials Science and Engineering, Technion-Israel Institute of Technology, 3200003 Haifa, Israel
Jungbluth A:
Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA
de Torres C:
Institut de Recerca Sant Joan de Déu, 08950 Barcelona, Spain
Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Deu, 08950 Barcelona, Spain
Lavarino C:
Institut de Recerca Sant Joan de Déu, 08950 Barcelona, Spain
Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Deu, 08950 Barcelona, Spain
Cheung NV:
Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA
Mora J:
Institut de Recerca Sant Joan de Déu, 08950 Barcelona, Spain
Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Deu, 08950 Barcelona, Spain
Sosnik A:
Laboratory of Pharmaceutical Nanomaterials Science, Department of Materials Science and Engineering, Technion-Israel Institute of Technology, 3200003 Haifa, Israel
Carcaboso AM:
Institut de Recerca Sant Joan de Déu, 08950 Barcelona, Spain
Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Deu, 08950 Barcelona, Spain.
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