Magnetic antibody-linked nanomatchmakers for therapeutic cell targeting.

Magnetic antibody-linked nanomatchmakers for therapeutic cell targeting.
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DOI:
10.1038/ncomms5880
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发表时间:
2014-09-10
影响因子:
16.6
通讯作者:
Marban, Eduardo
Marban, Eduardo
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Cheng, Ke;Shen, Deliang;Hensley, M. Taylor;Middleton, Ryan;Sun, Baiming;Liu, Weixin;De Couto, Geoffrey;Marban, Eduardo

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干细胞移植是治疗性心脏再生的一种有前途的策略,但目前的治疗方法受到潜在有益细胞(外源性移植或内源性募集)与受损组织之间低效相互作用的限制。在这里,我们应用靶向纳米医学来实现体内细胞介导的组织修复,成像和局部富集,而无需细胞移植。铁纳米颗粒与两种类型的抗体(一种针对治疗细胞上的抗原,另一种针对受损细胞)结合,以产生磁性双功能细胞标记物(MagBICE)。抗体将治疗细胞与受损细胞连接起来,而MagBICE的铁核心可以实现物理富集和成像。我们通过靶向外源性骨髓源性干细胞(表达CD 45)或内源性CD 34阳性细胞至受损心肌细胞(表达肌球蛋白轻链)治疗急性心肌梗死。通过磁吸引可以进一步增强靶向,从而增加功能益处。MagBICE代表了再生医学的通用平台技术。 细胞治疗需要足够量的治疗细胞被递送到受伤的组织。在这里,作者使用磁性铁纳米颗粒与结合治疗细胞和心肌细胞的抗体结合来治疗大鼠心肌缺血/再灌注损伤,并表明在局部应用磁场后增强了对心脏的靶向作用。
Stem cell transplantation is a promising strategy for therapeutic cardiac regeneration, but current therapies are limited by inefficient interaction between potentially beneficial cells (either exogenously transplanted or endogenously recruited) and the injured tissue. Here we apply targeted nanomedicine to achieve in vivo cell-mediated tissue repair, imaging and localized enrichment without cellular transplantation. Iron nanoparticles are conjugated with two types of antibodies (one against antigens on therapeutic cells and the other directed at injured cells) to produce magnetic bifunctional cell engager (MagBICE). The antibodies link the therapeutic cells to the injured cells, whereas the iron core of MagBICE enables physical enrichment and imaging. We treat acute myocardial infarction by targeting exogenous bone marrow-derived stem cells (expressing CD45) or endogenous CD34-positive cells to injured cardiomyocytes (expressing myosin light chain. Targeting can be further enhanced by magnetic attraction, leading to augmented functional benefits. MagBICE represents a generalizable platform technology for regenerative medicine. Cell therapy requires sufficient amounts of therapeutic cells to be delivered to the injured tissue. Here the authors use magnetic iron nanoparticles conjugated with antibodies that bind therapeutic cells and cardiomyocytes to treat myocardial ischemia/reperfusion injury in rats and show that targeting to the heart is enhanced upon local application of a magnetic field.
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