Synthesis of L-DOPA conjugated doxorubicin-polyethylenimine nanocarrier and evaluation of its cytotoxicity on A375 and HepG2 cell lines

IF 1.4 Q4 NANOSCIENCE & NANOTECHNOLOGY
Kimia Mansouri, F. Ahmadi, A. Dehshahri
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引用次数: 0

Abstract

Objective(s): Polyethylenimine (PEI) is one of the most-extensively investigated cationic polymers for gene and drug delivery. Recently, great attention has been directed to design of carriers for co-delivery of nucleic acids and small molecules. These delivery systems are able to overcome the limitations of gene or drug delivery alone. The aim of this study is to prepare a targeted nano-carrier for co-delivery of doxorubicin (Dox) and gene using polyethylenimine. Materials and Methods: In order to prepare the ligand-containing polymer conjugates, succinic anhydride was conjugated onto the hydroxyl group of Dox through an ester bond following the protection of Dox amines by Fmoc. Drug-polymer conjugates were then coupled with L-DOPA in order to prepare the targeted nanocarriers to the cells through Large Amino Acid Transporter-1 (LAT-1). The PEI derivatives were characterized using 1H-NMR. The toxicity of conjugated polymer, Dox and PEI was assessed on HepG2 and A375 cell lines with different expression level of LAT-1 transporters using MTT assay. Results: The chemical structure of PEI conjugate was confirmed by 1H-NMR. The cytotoxicity measurement demonstrated a cell line-dependent toxicity profile at the concentrations tested in this study. It was shown that there was no significant difference in cell-induced toxicity between conjugated polymer and its parent form in A375 cell line while the cytotoxicity of conjugated polymer was significantly lower than the parent PEI in HepG2 cells.Conclusion: These results provide promising evidence for further evaluation of PEI conjugate for co-delivery of drug and gene via LAT-1 transporters.
L-DOPA偶联阿霉素-聚乙烯亚胺纳米载体的合成及其对A375和HepG2细胞的细胞毒性评价
目的:聚乙烯亚胺(PEI)是研究最广泛的用于基因和药物递送的阳离子聚合物之一。近年来,用于核酸和小分子共递送的载体的设计受到了极大的关注。这些递送系统能够单独克服基因或药物递送的限制。本研究的目的是制备一种靶向纳米载体,用于使用聚乙烯亚胺共递送阿霉素(Dox)和基因。材料和方法:为了制备含配体的聚合物偶联物,在Fmoc保护Dox胺后,通过酯键将琥珀酸酐偶联到Dox的羟基上。然后将药物-聚合物偶联物与L-DOPA偶联,以制备通过大氨基酸转运蛋白-1(LAT-1)到达细胞的靶向纳米载体。使用1H-NMR对PEI衍生物进行表征。使用MTT法评估偶联聚合物、Dox和PEI对具有不同LAT-1转运蛋白表达水平的HepG2和A375细胞系的毒性。结果:用1H-NMR确证了PEI偶联物的化学结构。细胞毒性测量表明,在本研究中测试的浓度下,细胞系具有依赖性毒性。结果表明,在A375细胞系中,偶联聚合物与其亲代形式的细胞诱导毒性没有显著差异,而在HepG2细胞中偶联聚合物的细胞毒性显著低于亲代PEI。结论:这些结果为进一步评价PEI偶联物通过LAT-1转运蛋白共递送药物和基因提供了有希望的证据。
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来源期刊
Nanomedicine Journal
Nanomedicine Journal NANOSCIENCE & NANOTECHNOLOGY-
CiteScore
3.40
自引率
0.00%
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0
审稿时长
12 weeks
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