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 Journal Article

   

Authors:	Monterrubio, C.; Paco, S.; Olaciregui, N. G.; Pascual-Pasto, G.; Vila-Ubach, M.; Cuadrado-Vilanova, M.; Ferrandiz, M. M.; Castillo-Ecija, H.; Glisoni, R.; Kuplennik, N.; Jungbluth, A.; de Torres, C.; Lavarino, C.; Cheung, N. K. V.; Mora, J.; Sosnik, A.; Carcaboso, A. M.
Article Title:	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
Abstract:	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. © 2017 Elsevier B.V.
Keywords:	monoclonal antibodies; irinotecan; drug distribution; neuroblastoma; tumors; nanoparticles; body fluids; antibodies; mammals; extracellular fluid; neuroblastomas; targeted drug delivery; microdialysis; dialysis; biological materials; pdx models; gd2-targeted nanoparticles; intratumor drug distribution; irinotecan/sn-38; tumor extracellular fluid; micro-dialysis; targeted nanoparticle
Journal Title:	Journal of Controlled Release
Volume:	255
ISSN:	0168-3659
Publisher:	Elsevier B.V.
Date Published:	2017-06-10
Start Page:	108
End Page:	119
Language:	English
DOI:	10.1016/j.jconrel.2017.04.016
PROVIDER:	scopus
PUBMED:	28412222
PMCID:	PMC5564453
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85017525266&doi=10.1016%2fj.jconrel.2017.04.016&partnerID=40&md5=4a3e5b6a2fb4d5510f37e1753fd5f1be
Notes:	Article -- Export Date: 2 May 2017 -- Source: Scopus

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