Characterization of high-affinity peptides and their feasibility for use in nanotherapeutics targeting leukemia stem cells
Characterization of high-affinity peptides and their feasibility for use in nanotherapeutics targeting leukemia stem cells
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DOI：
10.1016/j.nano.2011.12.004
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发表时间：
2012-10-01
影响因子：
5.4
通讯作者：
Pan, Chong-xian
中科院分区：
文献类型：
--
作者：
Zhang, Hongyong;Luo, Juntao;Pan, Chong-xian
鉴定了具有LR（S/T）基序的肽，其可以特异性结合C型凝集素样分子-1（CLL 1），CLL 1是优先在急性髓性白血病干细胞（LSC）上表达的蛋白质。胶束纳米粒子共价修饰CLL 1靶向肽靶向药物输送。所得肽包覆的纳米颗粒直径为13.5 nm，并且每20 mg末端树枝状聚合物可负载5 mg柔红霉素。这些“靶向纳米胶束”将药物负载转运到表达CLL 1的细胞内部和从体外临床标本中分离的LSC，但不与正常血液或正常造血干细胞结合。与未修饰的纳米胶束相比，纳米胶束表面上CLL 1靶向肽的存在使得能够改善结合并将实质上更多的柔红霉素递送到表达CLL 1的细胞和CD 34（+）白血病细胞中。总之，用CLL 1靶向肽包被的纳米胶束对于根除LSCs和改善白血病治疗是潜在有用的。来自临床编辑：用靶向肽共价修饰的胶束纳米颗粒被用于柔红霉素的靶向药物递送以解决急性髓性白血病干细胞。(C)2012 Elsevier Inc. All rights reserved.
Peptides featuring the LR(S/T) motif were identified that could specifically bind to the C-type lectin-like molecule-1 (CLL1), a protein preferentially expressed on acute myeloid leukemia stem cells (LSCs). Micellar nanoparticles were covalently decorated with CLL1-targeting peptides for targeted drug delivery. The resulting peptide-coated nanoparticles were 13.5 nm in diameter and could be loaded with 5 mg of daunorubicin per 20 mg of telodendrimers. These "targeting nanomicelles" transported the drug load to the interior of cells expressing CLL1 and to LSCs isolated from clinical specimens in vitro, but did not bind to normal blood or normal hematopoietic stem cells. The presence of CLL1 targeting peptides on the surface of the nanomicelles enabled the improved binding and delivery of substantially more daunorubicin into the cells expressing CLL1 and CD34(+) leukemic cells compared with unmodified nanomicelles. In conclusion, nanomicelles coated with CLL1-targeting peptides are potentially useful for eradicating LSCs and improving leukemia therapy.From the Clinical Editor: Micellar nanoparticles covalently decorated with targeting peptides were used for targeted drug delivery of daunorubicin to address acute myeloid leukemia stem cells. (C) 2012 Elsevier Inc. All rights reserved.