Specific targeting to B cells by lipid-based nanoparticles conjugated with a novel CD22-ScFv.
Specific targeting to B cells by lipid-based nanoparticles conjugated with a novel CD22-ScFv.
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DOI：
10.1016/j.yexmp.2010.01.006
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发表时间：
2010-04
影响因子：
3.6
通讯作者：
Puri, Anu
中科院分区：
文献类型：
--
作者：
Loomis, Kristin;Smith, Brandon;Feng, Yang;Garg, Himanshu;Yavlovich, Amichai;Campbell-Massa, Ryan;Dimitrov, Dimiter S.;Blumenthal, Robert;Xiao, Xiaodong;Puri, Anu
CD 22抗原是B细胞淋巴瘤治疗干预的可行靶点。目前正在临床环境中研究几种治疗性抗CD 22抗体以及基于抗CD 22的免疫毒素（HA 22）。抗CD 22试剂与纳米药物递送载体的偶联预计将显著提高治疗效果。因此，我们产生了HA 22的靶向区段的突变体（CD 22 scFv）以增加其可溶性表达（mut-HA 22），并将其缀合到超声处理的脂质体的表面以产生免疫脂质体（mut-HA 22-脂质体）。我们使用钙黄绿素和/或罗丹明PE标记的脂质体研究了脂质体结合和CD 22 + B淋巴细胞（BJAB）的摄取。我们还测试了多柔比星脂质体对细胞毒性的靶向作用。我们报告：（i）mut-HA 22-脂质体与BJAB细胞的结合显著大于未与mut-HA 22缀合的脂质体（ii）这种结合通过与细胞CD 22的相互作用发生，因为细胞与mut-HA 22的预孵育阻断了随后的脂质体结合;（iii）mut-HA 22-脂质体在37°C而不是在4°C的细胞内定位表明，我们的靶向脂质体通过能量依赖性过程经由受体介导的内吞作用被摄取;和（iv）与对照脂质体相比，装载有多柔比星的Mut-HA 22-脂质体在BJAB细胞中表现出多柔比星的至少2-3倍的积累。此外，这些脂质体显示出对BJAB或Raji细胞（CD 22+）的至少2-4倍增强的杀伤，但对SUP-T1细胞（CD 22-）没有增强。总之，这些数据表明，这些第二代脂质体可以作为有前途的载体靶向药物输送治疗患者患有B细胞淋巴瘤。
The CD22 antigen is a viable target for therapeutic intervention for B-cell lymphomas. Several therapeutic anti-CD22 antibodies as well as an anti-CD22-based immunotoxin (HA22) are currently under investigation in clinical settings. Coupling of anti-CD22 reagents with a nano-drug delivery vehicle is projected to significantly improve treatment efficacies. Therefore, we generated a mutant of the targeting segment of HA22 (a CD22 scFv) to increase its soluble expression (mut-HA22), and conjugated it to the surface of sonicated liposomes to generate immunoliposomes (mut-HA22-liposomes). We examined liposome binding and uptake by CD22+ B-lymphocytes (BJAB) by using calcein and/or rhodamine PE-labeled liposomes. We also tested the effect of targeting on cellular toxicity with doxorubicin-loaded liposomes. We report that: (i) Binding of mut-HA22-liposomes to BJAB cells was significantly greater than liposomes not conjugated with mut-HA22 (control liposomes), and mut-HA22-liposomes bind to and are taken in by BJAB cells in a dose and temperature-dependent manner, respectively; (ii) This binding occurred via the interaction with the cellular CD22 as pre-incubation of the cells with mut-HA22 blocked subsequent liposome binding; (iii) Intracellular localization of mut-HA22-liposomes at 37°C but not at 4°C indicated that our targeted liposomes were taken up through an energy dependent process via receptor-mediated endocytosis; and (iv) Mut-HA22-liposomes loaded with doxorubicin exhibited at least 2-3 fold more accumulation of doxorubicin in BJAB cells as compared to control liposomes. Moreover, these liposomes showed at least a 2-4 fold enhanced killing of BJAB or Raji cells (CD22+), but not SUP-T1 cells (CD22-). Taken together these data suggest that these 2nd-generation liposomes may serve as promising carriers for targeted drug delivery to treat patients suffering from B-cell lymphoma.
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影响因子：
11.2
作者：
Li, Zhuqing;Mahesh, Sankaranarayana P.;Nussenblatt, Robert B.
通讯作者：
Nussenblatt, Robert B.
影响因子：
2.9
作者：
Nellis, DF;Ekstrom, DL;Giardina, SL
通讯作者：
Giardina, SL
影响因子：
4.3
作者：
Furman, Richard R;Coleman, Morton;Leonard, John P
通讯作者：
Leonard, John P
DOI：
10.1016/0006-291x(87)91565-8
发表时间：
1987-06-30
影响因子：
3.1
作者：
HOUCK, KS;HUANG, L
通讯作者：
HUANG, L
影响因子：
4.5
作者：
Laginha, Kimberley M.;Moase, Elaine H.;Allen, T. M.
通讯作者：
Allen, T. M.