Inhibition of tumor growth and metastasis by a self-therapeutic nanoparticle
Inhibition of tumor growth and metastasis by a self-therapeutic nanoparticle
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DOI：
10.1073/pnas.1214547110
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发表时间：
2013-04-23
影响因子：
11.1
通讯作者：
Mukherjee, Priyabrata
中科院分区：
文献类型：
--
作者：
Arvizo, Rochelle R.;Saha, Sounik;Mukherjee, Priyabrata
虽然纳米技术的生物医学应用（通常涉及功能化纳米粒子）已经取得了重大进展，但未经修饰的纳米粒子的生物学特性仍未得到充分研究。在此，我们证明未经修饰的金纳米颗粒（AuNPs）通过废除mapk信号传导以大小和浓度依赖的方式抑制癌细胞的增殖。此外，这些aunp通过减少EMT相关蛋白的分泌，上调E-Cadherin，下调Snail、N-Cadherin和Vimentin，逆转癌细胞的上皮-间质转化（EMT）。在两种不同的原位卵巢癌模型中，抑制MAPK信号和逆转AuNP治疗后的EMT可抑制肿瘤生长和转移。肿瘤组织Western blot分析显示E-Cadherin上调，Snail和phospho-MAPK下调，证实了AuNP治疗后EMT的逆转和MAPK信号的抑制。单个自我治疗纳米颗粒消除多种生长因子的信号级联的能力是独特的，并有望作为潜在的抗肿瘤和抗转移剂在医学上应用。
Although biomedical applications of nanotechnology, which typically involve functionalized nanoparticles, have taken significant strides, biological characterization of unmodified nanoparticles remains underinvestigated. Herein we demonstrate that unmodified gold nanoparticles (AuNPs) inhibit the proliferation of cancer cells in a size-and concentration-dependent manner by abrogating MAPK-signaling. In addition, these AuNPs reverse epithelial-mesenchymal transition (EMT) in cancer cells by reducing secretion of a number of proteins involved in EMT, up-regulating E-Cadherin, and down-regulating Snail, N-Cadherin, and Vimentin. Inhibition of MAPK signaling and reversal of EMT upon AuNP treatment inhibits tumor growth and metastasis in two separate orthotopic models of ovarian cancer. Western blot analyses of tumor tissues reveal up-regulation of E-Cadherin and down-regulation of Snail and phospho-MAPK, confirming the reversal of EMT and inhibition of MAPK signaling upon AuNP treatment. The ability of a single self-therapeutic nanoparticle to abrogate signaling cascades of multiple growth factors is distinctive and purports possible medical applications as potential antitumor and antimetastatic agent.