Hyaluronic Acid-Functionalized Nanomicelles Enhance SAHA Efficacy in 3D Endometrial Cancer Models.
Hyaluronic Acid-Functionalized Nanomicelles Enhance SAHA Efficacy in 3D Endometrial Cancer Models.
复制标题
透明质酸功能化纳米胶束增强SAHA在子宫内膜癌3D模型中的疗效。
DOI：
10.3390/cancers13164032
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发表时间：
2021-08-10
期刊：
影响因子：
5.2
通讯作者：
Francis L
中科院分区：
文献类型：
--
作者：
Edwards K;Yao S;Pisano S;Feltracco V;Brusehafer K;Samanta S;Oommen OP;Gazze SA;Paravati R;Maddison H;Li C;Gonzalez D;Conlan RS;Francis L
癌症治疗的主要限制之一是药物与体内任何组织相互作用引起的副作用。患者健康和有效治疗疾病之间往往存在平衡。为了绕过这种平衡行为，纳米颗粒被用来直接向肿瘤提供治疗，充当“特洛伊木马”。已知子宫内膜癌比健康组织具有更多的细胞表面蛋白CD44。在这里，为了有效地靶向子宫内膜癌，天然结合CD44蛋白的透明质酸被附着在纳米颗粒的表面，并在微组织或球体上进行测试，以更好地模拟肿瘤并了解药物递送性能。我们表明，我们的透明质酸纳米颗粒制剂改善了药物作用，并与癌细胞相互作用，而不是没有这种靶向剂。组蛋白脱乙酰酶（HDAC）在癌症中上调，导致HDAC抑制化合物的开发，其中几种目前处于临床试验中。与毒性和非特异性靶向相关的副作用表明需要有效的药物递送方法和肿瘤特异性靶向以增强HDAC在实体瘤癌症中的功效。SAHA封装在用表面透明质酸部分官能化的F127胶束内，被开发用于靶向表达升高水平的CD44的子宫内膜癌细胞。在2D和3D模型中进行体外活力和形态分析，以评估该方法的转化潜力。包封增强了SAHA的递送和活性，证明了在2D和3D子宫内膜癌模型中增加的细胞毒性功效。高含量成像显示2D中纳米颗粒内化改善，3D模型中CD44渗透增强。此外，纳米递送系统增强球状体穿透，导致细胞生长抑制、p21相关的细胞周期停滞，以及克服在游离药物处理的II型子宫内膜癌细胞中观察到的EMT相关表型的形成。这项研究表明，SAHA的靶向纳米颗粒递送可以为改善其在子宫内膜癌中的疗效提供基础。使用子宫内膜癌的3D模型可以阐明纳米颗粒的性能和CD44靶向，可能是通过渗透和保留在肿瘤模型中。
One of the major limitations to cancer therapies are the side effects caused by the drug interacting with any tissue in the body. There is often a balance between patient health and effectively treating the disease. To by-pass this balancing act nanoparticles are being used to deliver therapeutics straight to the tumors, acting as “Trojan Horses”. Endometrial cancers are known to have more of the cell surface protein CD44 than healthy tissues. Here, to efficiently target endometrial cancer, hyaluronic acid, which naturally binds to the CD44 protein was attached to the surface of nanoparticles and tested on microtissues or spheroids to better model a tumor and understand drug delivery performance. We show that our hyaluronic acid-nanoparticle formulations improve drug effects and interact with the cancer cells more than without this targeting agent. Histone Deacetylase (HDAC) enzymes are upregulated in cancer leading to the development of HDAC inhibiting compounds, several of which are currently in clinical trials. Side effects associated with toxicity and non-specific targeting indicate the need for efficient drug delivery approaches and tumor specific targeting to enhance HDAC efficacy in solid tumor cancers. SAHA encapsulation within F127 micelles functionalized with a surface hyaluronic acid moiety, was developed to target endometrial cancer cells expressing elevated levels of CD44. In vitro viability and morphology analyses was conducted in both 2D and 3D models to assess the translational potential of this approach. Encapsulation enhanced SAHA delivery and activity, demonstrating increased cytotoxic efficacy in 2D and 3D endometrial cancer models. High-content imaging showed improved nanoparticle internalization in 2D and CD44 enhanced penetration in 3D models. In addition, the nano-delivery system enhanced spheroid penetration resulting in cell growth suppression, p21 associated cell cycle arrest, as well as overcoming the formation of an EMT associated phenotype observed in free drug treated type II endometrial cancer cells. This study demonstrates that targeted nanoparticle delivery of SAHA could provide the basis for improving its efficacy in endometrial cancer. Using 3D models for endometrial cancer allows the elucidation of nanoparticle performance and CD44 targeting, likely through penetration and retention within the tumor model.
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影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1016/j.jsbmb.2007.09.020
发表时间：
2008-02-01
影响因子：
4.1
作者：
Doll, A.;Abal, M.;Reventos, J.
通讯作者：
Reventos, J.
多乳酸 - 糖苷糖纳米颗粒，用于控制抗癌剂的递送。
影响因子：
8
作者：
Dinarvand R;Sepehri N;Manoochehri S;Rouhani H;Atyabi F
通讯作者：
Atyabi F
通过强制浮动和悬挂掉落方法获得药物筛查获得的3D膀胱肿瘤球体的比较分析。
影响因子：
4
作者：
Amaral RLF;Miranda M;Marcato PD;Swiech K
通讯作者：
Swiech K
影响因子：
--
作者：
Choi, Ki Young;Min, Kyung Hyun;Jeong, Seo Young
通讯作者：
Jeong, Seo Young