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载柔红霉素的四氧化三铁纳米粒通过半胱天冬氨酸蛋白酶 8-多聚(ADP-核糖)聚合酶途径诱导细胞凋亡,并抑制体内 K562 白血病细胞诱导的肿瘤生长。

Fe3O4 nanoparticles with daunorubicin induce apoptosis through caspase 8-PARP pathway and inhibit K562 leukemia cell-induced tumor growth in vivo.

机构信息

State Key Lab of Bioelectronics (Chien-Shiung Wu Lab), Department of Biological Science and Medical Engineering, Southeast University, Nanjing, China.

出版信息

Nanomedicine. 2011 Oct;7(5):595-603. doi: 10.1016/j.nano.2011.01.013. Epub 2011 Feb 17.

Abstract

Nanomaterials can enhance the delivery and treatment efficiency of anticancer drugs, but the mechanisms of the tumor-reducing activity of ferrous-ferric oxide (Fe(3)O(4)) nanoparticles (NPs) with daunorubicin (DNR) have not been established. Here we investigate the synergistic effects of Fe(3)O(4) NPs with DNR on the induction of apoptosis using K562 leukemia cells. Fe(3)O(4) NPs increased the ability of DNR to induce apoptosis in both adriamycin-sensitive and adriamycin-resistant K562 cells through the caspase 8-poly(ADP-ribose) polymerase pathway. Fe(3)O(4) NPs combined with DNR also effectively inhibited the tumor growth induced by the inoculation of K562 cells into nude mice. The increased cell apoptotic rate was closely correlated with the enhanced inhibition of tumor growth. Biodistribution studies in xenograft tumors indicated that Fe(3)O(4) NPs could be potentially excreted from the body via the gastrointestinal system. In conclusion, our study suggests that Fe(3)O(4) NPs combined with anticancer drugs could serve as a better alternative for targeted therapeutic approaches to cancer treatments.

摘要

纳米材料可以提高抗癌药物的递送和治疗效率,但亚铁-氧化铁(Fe3O4)纳米颗粒(NPs)与柔红霉素(DNR)协同降低肿瘤活性的机制尚未建立。在这里,我们研究了 Fe3O4 NPs 与 DNR 联合使用对 K562 白血病细胞凋亡诱导的协同作用。Fe3O4 NPs 通过半胱天冬酶 8-多聚(ADP-核糖)聚合酶途径增加了 DNR 在阿霉素敏感和阿霉素耐药 K562 细胞中诱导凋亡的能力。Fe3O4 NPs 与 DNR 联合使用还能有效抑制 K562 细胞接种入裸鼠后引起的肿瘤生长。细胞凋亡率的增加与肿瘤生长抑制的增强密切相关。异种移植肿瘤中的生物分布研究表明,Fe3O4 NPs 可能通过胃肠道系统从体内排出。总之,我们的研究表明,Fe3O4 NPs 与抗癌药物联合使用可能成为癌症治疗靶向治疗方法的更好选择。

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Anticancer therapy targeting the apoptotic pathway.针对凋亡途径的抗癌治疗。
Lancet Oncol. 2003 Dec;4(12):721-9. doi: 10.1016/s1470-2045(03)01277-4.
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Nanoparticles in cancer therapy and diagnosis.纳米颗粒在癌症治疗与诊断中的应用
Adv Drug Deliv Rev. 2002 Sep 13;54(5):631-51. doi: 10.1016/s0169-409x(02)00044-3.

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