Magnetic antibody-linked nanomatchmakers for therapeutic cell targeting

被引:117
作者
Cheng, Ke [1 ,2 ,3 ,4 ]
Shen, Deliang [5 ]
Hensley, M. Taylor [2 ]
Middleton, Ryan [1 ]
Sun, Baiming [1 ]
Liu, Weixin [1 ]
De Couto, Geoffrey [1 ]
Marban, Eduardo [1 ]
机构
[1] Cedars Sinai Heart Inst, Los Angeles, CA 90048 USA
[2] N Carolina State Univ, Coll Vet Med, Ctr Comparat Med & Translat Res, Dept Mol Biomed Sci, Raleigh, NC 27607 USA
[3] Univ N Carolina, Joint Dept Biomed Engn, Raleigh, NC 27607 USA
[4] Univ N Carolina, Raleigh, NC 27607 USA
[5] Zhengzhou Univ, Affiliated Hosp 1, Dept Cardiol, Zhengzhou 450052, Henan, Peoples R China
基金
美国国家卫生研究院;
关键词
CARDIOSPHERE-DERIVED CELLS; HEMATOPOIETIC STEM-CELLS; BISPECIFIC ANTIBODIES; MONONUCLEAR-CELLS; CARDIAC-FUNCTION; HEART; DELIVERY; REPAIR; RATS;
D O I
10.1038/ncomms5880
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
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.
引用
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页数:9
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