Format

Send to

Choose Destination
See comment in PubMed Commons below
J Control Release. 2017 Apr 12;255:108-119. doi: 10.1016/j.jconrel.2017.04.016. [Epub ahead of print]

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.

Author information

1
Institut de Recerca Sant Joan de Deu, 08950 Barcelona, Spain; Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Deu, 08950 Barcelona, Spain.
2
CONICET-Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, Universidad de Buenos Aires, CP1113 Buenos Aires, Argentina.
3
Laboratory of Pharmaceutical Nanomaterials Science, Department of Materials Science and Engineering, Technion-Israel Institute of Technology, 3200003 Haifa, Israel.
4
Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
5
Institut de Recerca Sant Joan de Deu, 08950 Barcelona, Spain; Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Deu, 08950 Barcelona, Spain. Electronic address: amontero@fsjd.org.

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.

KEYWORDS:

GD2-targeted nanoparticles; Intratumor drug distribution; Irinotecan (PubChem CID: 60838).; Irinotecan/SN-38; Microdialysis; Neuroblastoma; PDX models; SN-38 (PubChem CID: 104842); Tumor extracellular fluid

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center