The effect of co-delivery of paclitaxel and curcumin by transferrin-targeted PEG-PE-based mixed micelles on resistant ovarian cancer in 3-D spheroids and in vivo tumors.
The effect of co-delivery of paclitaxel and curcumin by transferrin-targeted PEG-PE-based mixed micelles on resistant ovarian cancer in 3-D spheroids and in vivo tumors.
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DOI：
10.1016/j.ejpb.2014.07.001
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发表时间：
2014-10
期刊：
影响因子：
--
通讯作者：
Torchilin VP
中科院分区：
文献类型：
--
作者：
Sarisozen C;Abouzeid AH;Torchilin VP
多细胞3D癌细胞培养物（球状体）在形状、细胞形态、生长动力学、基因表达和药物反应方面与体内肿瘤相似。然而，这些特征导致非常有限的药物渗透到球状体的更深部分。在这项研究中，我们使用多药耐药（MDR）卵巢癌细胞球体和体内肿瘤模型来评估紫杉醇（PCL）和一种有效的NF-κB抑制剂姜黄素（CUR）的共递送。将PCL和CUR共负载到以转铁蛋白（TF）为靶向配体修饰的聚乙二醇-磷脂酰乙醇胺（PEG-PE）聚合物胶束中。在球状体中研究了细胞毒性、细胞缔合和向更深层的积累，并与单层细胞培养进行了比较。与非靶向胶束相比，流式细胞术和共聚焦成像证明了具有TF靶向的球形体中的胶束渗透显著更深和更高。无论是在单层还是在球状体中，当在非靶向胶束中与CUR共同递送或在TF靶向胶束中作为单一药物时，PCL的细胞毒性均显着增加，而共负载胶束的TF修饰并未进一步增强细胞毒性。体内肿瘤抑制研究显示与3D细胞培养实验具有良好的相关性，这表明当前的球体模型可以用作评价靶向胶束中抗癌化合物共递送的中间模型。
Multicellular 3D cancer cell culture (spheroids) resemble to in vivo tumors in terms of shape, cell morphology, growth kinetics, gene expression and drug response. However, these characteristics cause very limited drug penetration into deeper parts of the spheroids. In this study, we used multi drug resistant (MDR) ovarian cancer cell spheroid and in vivo tumor models to evaluate the co-delivery of paclitaxel (PCL) and a potent NF-κB inhibitor curcumin (CUR). PCL and CUR were co-loaded into the polyethylene glycol-phosphatidyl ethanolamine (PEG-PE) based polymeric micelles modified with Transferrin (TF) as the targeting ligand. Cytotoxicity, cellular association and accumulation into the deeper layers were investigated in the spheroids and compared with the monolayer cell culture. Comparing to non-targeted micelles, flow cytometry and confocal imaging proved significantly deeper and higher micelle penetration into the spheroids with TF-targeting. Both in monolayers and spheroids, PCL cytotoxicity was significantly increased when co-delivered with CUR in non-targeted micelles or as single agent in TF-targeted micelles, whereas TF-modification of co-loaded micelles did not further enhance the cytotoxicity. In vivo tumor inhibition studies showed good correlation with the 3D cell culture experiments, which suggests the current spheroid model can be used as an intermediate model for evaluation of co-delivery of anticancer compounds in targeted micelles.
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影响因子：
3
作者：
Daniels, Tracy R.;Bernabeu, Ezequiel;Rodriguez, Jose A.;Patel, Shabnum;Kozman, Maggie;Chiappetta, Diego A.;Holler, Eggehard;Ljubimova, Julia Y.;Helguera, Gustavo;Penichet, Manuel L.
通讯作者：
Penichet, Manuel L.
DOI：
10.1038/mtna.2014.5
发表时间：
2014-03-11
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
通讯作者：
--
影响因子：
3
作者：
DURAND, RE
通讯作者：
DURAND, RE
影响因子：
56.9
作者：
Cukierman, E;Pankov, R;Yamada, KM
通讯作者：
Yamada, KM
影响因子：
5.8
作者：
Hall, MD;Martin, C;Callaghan, R
通讯作者：
Callaghan, R