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

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Article

Monterrubio, Carles^1,2  Paco, Sonia^1,2  Olaciregui, Nagore G.^1,2  Pascual-Pasto, Guillem^1,2  Vila-Ubach, Monica^1,2  Cuadrado-Vilanova, Maria^1,2  Mar Ferrandiz, M.^1,2  Castillo-Ecija, Helena^1,2  Glisoni, Romina³  Kuplennik, Nataliya⁴  Jungbluth, Achim⁵  de Torres, Carmen^1,2  Lavarino, Cinzia^1,2  Cheung, Nai-Kong V.⁵  Mora, Jaume^1,2  Sosnik, Alejandro⁴  Carcaboso, Angel M.^1,2 

[1] Inst Recerca St Joan de Deu, Santa Rosa 39-57, Barcelona 08950, Spain

[2] Hosp St Joan de Deu, Dept Pediat Hematol & Oncol, Barcelona 08950, Spain

[3] Univ Buenos Aires, Fac Pharm & Biochem, Dept Pharmaceut Technol, CONICET, RA-1113 Buenos Aires, DF, Argentina

[4] Technion Israel Inst Technol, Dept Mat Sci & Engn, Lab Pharmaceut Nanomat Sci, IL-3200003 Haifa, Israel

[5] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA

关键词: GD2-targeted nanoparticles;    Intratumor drug distribution;    Microdialysis;    Tumor extracellular fluid;    Neuroblastoma;    Irinotecan/SN-38;    PDX models;   

DOI  :  10.1016/j.jconrel.2017.04.016

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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