Anti-CD123 antibody-modified niosomes for targeted delivery of daunorubicin against acute myeloid leukemia.
Anti-CD123 antibody-modified niosomes for targeted delivery of daunorubicin against acute myeloid leukemia.
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抗 CD123 抗体修饰的囊泡用于针对急性髓系白血病靶向递送柔红霉素
DOI：
10.1080/10717544.2017.1333170
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发表时间：
2017-11
期刊：
影响因子：
6
通讯作者：
Li H
中科院分区：
文献类型：
--
作者：
Liu FR;Jin H;Wang Y;Chen C;Li M;Mao SJ;Wang Q;Li H
设计并研究了一种新型的用于靶向给药柔红霉素（DNR）治疗急性髓系白血病（AML）的囊泡给药系统。通过后插入方法将缀合至Mal-PEG 2000-DSPE的抗CD 123抗体掺入正常类脂质体（NS）中以提供抗体修饰的类脂质体（CD 123-NS）。接下来，用不同密度的抗体（0.5或2%，抗体/Span 80，摩尔比）修饰NS，从而提供L-CD 123-NS和H-CD 123-NS。我们研究了抗体浓度对NB 4和THP-1细胞中囊泡摄取效率的影响，在NB 4和THP-1细胞上，CD 123表达不同。我们的结果表明，在AML细胞中，CD 123-NS显示出比NS显著更高的摄取效率，并且CD 123-NS的摄取效率具有配体密度依赖性。此外，与对照相比，与抗CD 123抗体预孵育的AML细胞显示CD 123-NS的细胞摄取显着减少。对摄取机制的进一步研究证实了受体介导的内吞过程。在NB 4和THP-1细胞中，柔红霉素（DNR）负载的H-CD 123-NS的细胞毒性分别比DNR负载的NS高2.45倍和3.22倍。在用DNR-H-CD 123-NS治疗的白血病小鼠中观察到延长的存活时间。总的来说，这些发现支持CD 123-NS代表用于治疗AML的有前景的递送系统。
A novel niosomal delivery system was designed and investigated for the targeted delivery of daunorubicin (DNR) against acute myeloid leukemia (AML). Anti-CD123 antibodies conjugated to Mal-PEG2000-DSPE were incorporated into normal niosomes (NS) via a post insertion method to afford antibody-modified niosomes (CD123-NS). Next, NS was modified with varying densities of antibody (0.5 or 2%, antibody/Span 80, molar ratio), thus providing L-CD123-NS and H-CD123-NS. We studied the effect of antibody density on the uptake efficiency of niosomes in NB4 and THP-1 cells, on which CD123 express differently. Our results demonstrate CD123-NS showed significantly higher uptake efficiency than NS in AML cells, and the uptake efficiency of CD123-NS has been ligand density-dependent. Also, AML cells preincubated with anti-CD123 antibody showed significantly reduced cellular uptake of CD123-NS compared to control. Further study on the uptake mechanism confirmed a receptor-mediated endocytic process. Daunorubicin (DNR)-loaded H-CD123-NS demonstrated a 2.45- and 3.22-fold higher cytotoxicity, compared to DNR-loaded NS in NB4 and THP-1 cells, respectively. Prolonged survival time were observed in leukemic mice treated with DNR-H-CD123-NS. Collectively, these findings support that the CD123-NS represent a promising delivery system for the treatment of AML.
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影响因子：
3.5
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