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. Academic Article uri icon

Overview

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.

publication date

  • April 12, 2017

Research

keywords

  • Antibodies, Monoclonal
  • Antineoplastic Agents, Phytogenic
  • Camptothecin
  • Extracellular Fluid
  • Immunoglobulin G
  • N-Acetylgalactosaminyltransferases
  • Nanoparticles
  • Neuroblastoma

Identity

PubMed Central ID

  • PMC5564453

Scopus Document Identifier

  • 85017525266

Digital Object Identifier (DOI)

  • 10.1016/j.jconrel.2017.04.016

PubMed ID

  • 28412222

Additional Document Info

volume

  • 255