Nanocarrier-Based Delivery of SN22 as a Tocopheryl Oxamate Prodrug Achieves Rapid Tumor Regression and Extends Survival in High-Risk Neuroblastoma Models
作者:Ivan S. Alferiev、David T. Guerrero、Danielle Soberman、Peng Guan、Ferro Nguyen、Venkatadri Kolla、Ilia Fishbein、Blake B. Pressly、Garrett M. Brodeur、Michael Chorny
DOI:10.3390/ijms23031752
日期:——
cell killing potency, and overcoming drug resistance, nanocarrier-mediated delivery of topoisomerase I inhibitors of the camptothecin family has the potential to dramatically improve treatment efficacy and minimize side effects. In this study, a structurally enhanced camptothecin analog, SN22, reversibly coupled with a redox-silent tocol derivative (tocopheryl oxamate) to allow its optimally stable
尽管使用了强化的多模式治疗,但大多数高危神经母细胞瘤 (NB) 患者无法存活。如果给药策略没有显着改进,用作高危肿瘤一线治疗的抗癌药物通常无法在播散性、复发性或难治性疾病的情况下提供具有临床意义的结果。通过提高药理学选择性、有利地改变生物分布、增强肿瘤细胞杀伤能力和克服耐药性,纳米载体介导的喜树碱家族拓扑异构酶 I 抑制剂的递送有可能显着提高治疗效果并最大限度地减少副作用。在这项研究中,结构增强的喜树碱类似物 SN22,可逆地与氧化还原沉默的母育酚衍生物(生育酚草酸酯)结合,使其从聚乙二醇化的亚 100 nm 纳米颗粒 (NP) 中获得最佳稳定封装和受控释放,表现出强烈的 NB 细胞生长抑制活性,转化为快速消退和持久抑制再生原位、MYCN 扩增的 NB 肿瘤。在概括高危疾病不同阶段(诊断时与复发时,在强化多药化疗后获得性 p53 功能丧失时)的临床前模型中实现了强大的抗肿瘤作用和显着延长的生存期,证明了
[EN] PHOSPHAMIDE DERIVATIVE, METHOD FOR MANUFACTURING THE SAME, AND USES THEREOF<br/>[FR] DÉRIVÉ DE PHOSPHAMIDE, SON PROCÉDÉ DE FABRICATION ET SES UTILISATIONS<br/>[ZH] 一种磷酰胺衍生物及制备方法和用途
Comptothecin analogues, preparation methods therefor, use thereof as drugs, and pharmaceutical compositions containing said analogues
申请人:Societe de Conseils de Recherches et d'Applications Scientifiques (S.C.R.A.S.)
公开号:US06339091B1
公开(公告)日:2002-01-15
The compound of the formula
wherein the substituents are defined as in the specification and its non-toxic, pharmaceutically acceptable salts which are useful for the treatment of viral infections, parasitic diseases and the treatment of cancer.