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

Monterrubio, Carles
Paco, Sonia
Olaciregui, Nagore G.
Pascual Pasto, Guillem
Vila Ubach, Monica
Cuadrado Vilanova, Maria
Ferrandiz, M. Mar
Castillo Ecija, Helena
Glisoni, Romina Julieta
Kuplennik, Nataliya
Jungbluth, Achim
de Torres, Carmen
Lavarino, Cinzia
Cheung, N. K. V.
Mora, Jaume
Sosnik, Alejandro Dario
Montero Carcaboso, Angel

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Publication date

June 2017

DOI

10.1016/j.jconrel.2017.04.016

Publisher

Elsevier BV

ISSN

0168-3659

Journal

Journal of Controlled Release

Citation count (estimate)

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 c...