Core-shell nanoparticle-based peptide therapeutics and combined hyperthermia for enhanced cancer cell apoptosis.
Core-shell nanoparticle-based peptide therapeutics and combined hyperthermia for enhanced cancer cell apoptosis.
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DOI：
10.1021/nn503431x
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发表时间：
2014-09-23
期刊：
影响因子：
17.1
通讯作者：
Lee, Ki-Bum
中科院分区：
文献类型：
--
作者：
Shah, Birju P.;Pasquale, Nicholas;De, Gejing;Tan, Tao;Ma, Jianjie;Lee, Ki-Bum
关键词：
近年来，线粒体靶向肽作为潜在的化疗药物引起了人们极大的兴趣。然而，显然需要开发策略来克服肽的关键限制，例如溶解性差和缺乏靶特异性，这阻碍了它们的临床应用。为此，我们报告磁性核-壳纳米颗粒（MCNP）介导的递送靶向促凋亡的两亲性尾锚定肽（ATAP）到恶性脑和转移性乳腺癌细胞。ATAP与MCNP的缀合显著增强了ATAP的化疗功效，而靶向配体的存在提供了对癌细胞的选择性递送。MCNP介导的热疗的诱导进一步增强了ATAP的功效。总之，MCNP介导的ATAP递送和随后的热疗的组合导致对线粒体功能障碍的增强作用，从而导致癌细胞凋亡增加。
Mitochondria-targeting peptides have garnered immense interest as potential chemotherapeutics in recent years. However, there is a clear need to develop strategies to overcome the critical limitations of peptides, such as poor solubility and the lack of target specificity, which impede their clinical applications. To this end, we report magnetic core–shell nanoparticle (MCNP)-mediated delivery of a mitochondria-targeting pro-apoptotic amphipathic tail-anchoring peptide (ATAP) to malignant brain and metastatic breast cancer cells. Conjugation of ATAP to the MCNPs significantly enhanced the chemotherapeutic efficacy of ATAP, while the presence of targeting ligands afforded selective delivery to cancer cells. Induction of MCNP-mediated hyperthermia further potentiated the efficacy of ATAP. In summary, a combination of MCNP-mediated ATAP delivery and subsequent hyperthermia resulted in an enhanced effect on mitochondrial dysfunction, thus resulting in increased cancer cell apoptosis.
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影响因子：
4.6
作者：
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通讯作者：
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影响因子：
11.2
作者：
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DOI：
10.1073/pnas.1114518108
发表时间：
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影响因子：
11.1
作者：
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通讯作者：
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影响因子：
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作者：
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