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J Control Release ; 255: 108-119, 2017 06 10.
Article in English | MEDLINE | ID: mdl-28412222

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.


Subject(s)
Antibodies, Monoclonal/administration & dosage , Antineoplastic Agents, Phytogenic/administration & dosage , Camptothecin/analogs & derivatives , Extracellular Fluid/metabolism , Immunoglobulin G/administration & dosage , N-Acetylgalactosaminyltransferases/antagonists & inhibitors , Nanoparticles/administration & dosage , Neuroblastoma/metabolism , Animals , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal, Murine-Derived , Antigens, Neoplasm/genetics , Antigens, Neoplasm/metabolism , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacokinetics , Camptothecin/administration & dosage , Camptothecin/chemistry , Camptothecin/pharmacokinetics , Cell Line, Tumor , Child, Preschool , Drug Liberation , Gene Expression Regulation, Neoplastic , Humans , Immunoglobulin G/chemistry , Irinotecan , Male , Mice, Nude , N-Acetylgalactosaminyltransferases/genetics , N-Acetylgalactosaminyltransferases/immunology , N-Acetylgalactosaminyltransferases/metabolism , Nanoparticles/chemistry , Neuroblastoma/drug therapy , Tissue Distribution , Xenograft Model Antitumor Assays
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