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

被引：34
作者：
Iyer, Radhika [1 ]
Croucher, Jamie L. [1 ]
Chorny, Michael [2 ,3 ]
Mangino, Jennifer L. [1 ]
Alferiev, Ivan S. [2 ,3 ]
Levy, Robert J. [2 ,3 ]
Kolla, Venkatadri [1 ]
Brodeur, Garrett M. [1 ,3 ]
机构：
[1] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA
[2] Childrens Hosp Philadelphia, Div Cardiol, Philadelphia, PA 19104 USA
[3] Perelman Sch Med, Dept Pediat, Philadelphia, PA 19104 USA
来源：
CANCER LETTERS | 2015年 / 360卷 / 02期
关键词：
Irinotecan; Nanoparticles; Neuroblastoma; SN38; Tocopherol succinate; HIGH-RISK NEUROBLASTOMA; PHASE-I TRIAL; THERAPY CONSORTIUM; ANTITUMOR EFFICACY; ORAL IRINOTECAN; DRUG-DELIVERY; SOLID TUMORS; PHARMACOKINETICS; CANCER; SN-38;
D O I：
10.1016/j.canlet.2015.02.011
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
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 200x 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. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码：205 / 212
页数：8
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