期刊
JOURNAL OF CONTROLLED RELEASE
卷 255, 期 -, 页码 108-119出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2017.04.016
关键词
GD2-targeted nanoparticles; Intratumor drug distribution; Microdialysis; Tumor extracellular fluid; Neuroblastoma; Irinotecan/SN-38; PDX models
资金
- AECC Scientific Foundation
- MINECO [SAF2011-22660, PRI-AIBAR-2011-0977]
- Fundacion BBVA [152/2011]
- European Union Seventh Framework Programme under Marie Curie International Reintegration [PIRG-08-GA-2010-276998]
- ISCIII-FEDER [CP13/00189]
- Russell Berrie Nanotechnology Institute (Technion)
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.
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