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首页> 外文期刊>Journal of biomedical materials research, Part A >Folic acid conjugated polymeric drug delivery vehicle for targeted cancer detection in hepatocellular carcinoma
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Folic acid conjugated polymeric drug delivery vehicle for targeted cancer detection in hepatocellular carcinoma

机译：用于肝细胞癌的靶癌症检测的叶酸共轭聚合物药物递送载体

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摘要

Abstract Targeted therapies provide increased efficiency for the detection and treatment of cancer with reduced side effects. Folate receptor (alpha subunit) is overexpressed in multiple tumors including liver cancer. In this study, we evaluated the specificity and toxicity of a folic acid‐containing drug delivery vehicle (DDV) in a hepatocellular carcinoma (HCC) model. The DDV was prepared with two units each of folic acid (FA) and fluorescein isothiocyanate (FITC) molecules and conjugated to a central poly (ethylene glycol) (PEG) core via a modified chemo‐enzymatic synthetic process. Rat hepatoma (N1S1) and human monocytic (U937) cell lines were used for cell culture‐based assays and tested for DDV uptake and toxicity. Folate receptor expressions in liver tissues and cell lines were verified using standard immunohistochemistry techniques. Rat HCC model was used for in vivo assessment. The DDV was injected via intra‐arterial or intravenous methods and imaged with IVIS spectrum in vivo imaging system. Strong signals of FITC in the liver tumor region correlated to targeted DDV uptake. The use of PEG enhanced water‐solubility and provided flexibility for the interaction of FA ligands with multiple cell surface folate receptors that resulted in increased specific uptake. Our study suggested that PEG incorporation and folate targeting via intra‐arterial approach is an efficient strategy for targeted delivery in HCC therapy.
机译：摘要靶向疗法为患有副作用减少的癌症的检测和治疗提供了提高的效率。叶酸受体（α亚基）在包括肝癌的多种肿瘤中过表达。在该研究中，我们在肝细胞癌（HCC）模型中评估了含叶酸的药物递送载体（DDV）的特异性和毒性。用两种单位制备DDV，每种叶酸（FA）和荧光素异硫氰酸酯（FITC）分子，并通过改性的化学酶合成方法与中央聚（乙二醇）（PEG）核缀合。大鼠肝癌（N1S1）和人单核细胞（U937）细胞系用于细胞培养基测定并测试DDV吸收和毒性。使用标准免疫组织化学技术验证肝组织和细胞系中的叶酸受体表达。大鼠HCC模型用于体内评估。通过动脉内或静脉内方法注射DDV并用体内成像系统中的IVIS光谱进行成像。 FITC在肝脏肿瘤区域中的强信号与靶向DDV摄取相关。使用PEG增强的水溶性并为FA配体与多个细胞表面叶酸受体的相互作用提供了柔韧性，该受体导致具有增加的特异性摄取。我们的研究表明，PEG掺入和通过动脉内方法靶向的靶向是HCC治疗中靶向递送的有效策略。

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