Complex Structured Fluorescent Polythiophene Graft Copolymer as a Versatile Tool for Imaging, Targeted Delivery of Paclitaxel, and Radiotherapy
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- 作者：Emine Guler ; Huseyin Akbulut ; Caner Geyik ; Tulay Yilmaz ; Z. Pinar Gumus ; F. Baris Barlas ; Recep Erdem Ahan ; Dilek Odaci Demirkol ; Shuhei Yamada ; Takeshi Endo ; Suna Timur ; Yusuf Yagci
- 刊名：Biomacromolecules
- 出版年：2016
- 出版时间：July 11, 2016
- 年：2016
- 卷：17
- 期：7
- 页码：2399-2408
- 全文大小：685K
- 年卷期：0
- ISSN：1526-4602
文摘
Advances in polymer chemistry resulted in substantial interest to utilize their diverse intrinsic advantages for biomedical research. Especially, studies on drug delivery for tumors have increased to a great extent. In this study, a novel fluorescent graft copolymer has been modified by a drug and targeting moiety and the resulting structure has been characterized by alterations in fluorescent intensity. The polythiophene based hybrid graft copolymer was synthesized by successive organic reactions and combination of in situ N-carboxy anhydride (NCA) ring opening and Suzuki coupling polymerization processes. Initially, targeted delivery of the graft copolymer was investigated by introducing a tumor specific ligand, anti-HER2/neu antibody, on the structure. The functionalized polymer was able to differentially indicate HER2-expressing A549 human lung carcinoma cells, whereas no signal was obtained for Vero, monkey kidney epithelial cells, and HeLa, human cervix adenocarcinoma cells. After integrating paclitaxel into the structure, cell viability, cell cycle progression, and radiosensitivity studies demonstrate HER2/neu targeting polymers were most effective to inhibit cell proliferation. Importantly, the graft copolymer used had no cytotoxic effects to cells, as evidenced by cell viability and cell cycle analysis. This work clearly confirms that a specially designed and fabricated graft copolymer with a highly complex structure is a promising theranostic agent capable of targeting tumor cells for diagnostic and therapeutic purposes.