EGFR-Targeted Polymeric Mixed Micelles Carrying Gemcitabine for Treating Pancreatic Cancer.
EGFR-Targeted Polymeric Mixed Micelles Carrying Gemcitabine for Treating Pancreatic Cancer.
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DOI：
10.1021/acs.biomac.5b01419
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发表时间：
2016-01-11
影响因子：
6.2
通讯作者：
Mahato RI
中科院分区：
文献类型：
--
作者：
Mondal G;Kumar V;Shukla SK;Singh PK;Mahato RI
这项研究的目的是设计GE11肽（YhwygyTPQNVI），将聚（乙二醇） - 块的胶束连接起来的胶束 - 块状胶片（2-甲基-2-甲基-2-甲基-2-羧酸丙二醇 - 碳酸苯甲酸 - 丙二醇 - 乙二甲酸 - 甲甲苯甲苯甲苯甲苯甲苯甲苯；胰腺癌细胞混合胶束在全身施用后24小时优先积聚在原位胰腺肿瘤和肿瘤脉络膜上，与无效的混合胶束相比，GE11连接的混合胶束抑制了原位胰腺肿瘤的生长。通过免疫组织化学染色确定的细胞和内皮细胞。总之，GE11连接的混合胶束是治疗EGFR过表达癌症的有前途的方法。
The objective of this study was to design GE11 peptide (YHWYGYTPQNVI) linked micelles of poly(ethylene glycol)-block-poly(2-methyl-2-carboxyl-propylene carbonate-graft-gemcitabine-graft-dodecanol (PEG-b-PCC-g-GEM-g-DC) for enhanced stability and target specificity of gemcitabine (GEM) to EGFR-positive pancreatic cancer cells. GE11-PEG-PCD/mPEG-b-PCC-g-GEM-g-DC mixed micelles showed EGFR-dependent enhanced cellular uptake, and cytotoxicity as compared to scrambled peptide HW12-PEG-PCD/mPEG-b-PCC-g-GEM-g-DC mixed micelles and unmodified mPEG-b-PCC-g-GEM-g-DC micelles. Importantly, GE11-linked mixed micelles preferentially accumulated in orthotopic pancreatic tumor and tumor vasculature at 24 h post systemic administration. GE11-linked mixed micelles inhibited orthotopic pancreatic tumor growth compared to HW12-linked mixed micelles, unmodified mPEG-b-PCC-g-GEM-g-DC micelles, and free GEM formulations. Tumor growth inhibition was mediated by apoptosis of tumor cells and endothelial cells as determined by immunohistochemical staining. In summary, GE11-linked mixed micelles is a promising approach to treat EGFR overexpressing cancers.