Nanoparticle delivery of an SN38 conjugate is more effective than irinotecan in a mouse model of neuroblastoma.

Journal Article (Journal Article)

Neuroblastoma (NB) is the most common and deadly solid tumor in children. The majority of NB patients have advanced stage disease with poor prognosis, so more effective, less toxic therapy is needed. We developed a novel nanocarrier-based strategy for tumor-targeted delivery of a prodrug of SN38, the active metabolite of irinotecan. We formulated ultrasmall-sized (<100 nm) biodegradable poly(lactide)-poly(ethylene glycol) based nanoparticles (NPs) containing SN38 conjugated to tocopherol succinate (SN38-TS). Alternative dosing schedules of SN38-TS NPs were compared to irinotecan. Comparison of SN38-TS NPs (2 doses) with irinotecan (20 doses) showed equivalent efficacy but no cures. Comparison of SN38-TS NPs (8, 8, and 16 doses, respectively) to irinotecan (40 doses) showed that all SN38-TS NP regimens were far superior to irinotecan, and "cures" were obtained in all NP arms. SN38-TS NP delivery resulted in 200× the amount of SN38 in NB tumors at 4 hr post-treatment, compared to SN38 detected for the irinotecan arm; no toxicity was seen with NPs. We conclude that this SN38-TS NP formulation improved delivery, retention, and efficacy, without causing systemic toxicity.

Full Text

Duke Authors

Cited Authors

  • Iyer, R; Croucher, JL; Chorny, M; Mangino, JL; Alferiev, IS; Levy, RJ; Kolla, V; Brodeur, GM

Published Date

  • May 2015

Published In

Volume / Issue

  • 360 / 2

Start / End Page

  • 205 - 212

PubMed ID

  • 25684664

Pubmed Central ID

  • PMC4361245

Electronic International Standard Serial Number (EISSN)

  • 1872-7980

International Standard Serial Number (ISSN)

  • 0304-3835

Digital Object Identifier (DOI)

  • 10.1016/j.canlet.2015.02.011


  • eng