Extracellular vesicles derived from dental mesenchymal stem/stromal cells with gemcitabine as a cargo have an inhibitory effect on the growth of pancreatic carcinoma cell lines in vitro

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS
Daniela Klimova , Jana Jakubechova , Ursula Altanerova , Andreas Nicodemou , Jakub Styk , Tomas Szemes , Vanda Repiska , Cestmir Altaner
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引用次数: 6

Abstract

Extracellular vesicles (EVs) are nowadays a target of interest in cancer therapy as a successful drug delivering tool. Based on their many beneficial biocompatible properties are designed to transport nucleic acids, proteins, various nanomaterials or chemotherapeutics. Extracellular vesicles derived from mesenchymal stem/stromal cells (MSCs) possess their tumor-homing abilities. This inspired us to engineer the MSC's EVs to be packed with chemotherapeutic agents and deliver it as a Trojan horse directly into tumor cells. In our study, human dental pulp MSCs (DP-MSCs) were cultivated with gemcitabine (GCB), which led to its absorption by the cells and subsequent secretion of the drug out into conditioned media in EVs. Concentrated conditioned media containing small EVs (potentially exosomes) significantly inhibited the cell growth of pancreatic carcinoma cell lines in vitro. DP-MSCs were simultaneously engineered to express a suicide gene fused yeast cytosinedeaminase:uracilphosphoribosyltransferase (yCD::UPRT). The product of the suicide gene converts non-toxic prodrug 5-fluorocytosine (5-FC) to highly cytotoxic chemotherapeutic drug 5-fluorouracil (5-FU) in the recipient cancer cells. Conversion of 5-FC to 5-FU had an additional effect on cancer cell's growth inhibition. Our results showed a therapeutic potential for DP-MSC-EVs to be designed for successful delivering of chemotherapeutic drugs, together with prodrug suicide gene therapy system.

以吉西他滨为载体的口腔间充质干细胞/基质细胞衍生的细胞外小泡对胰腺癌细胞系的生长具有抑制作用
细胞外囊泡(EVs)作为一种成功的药物递送工具,目前是癌症治疗中的一个感兴趣的靶点。基于其许多有益的生物相容性特性,设计用于运输核酸、蛋白质、各种纳米材料或化疗药物。来源于间充质干细胞/基质细胞的细胞外小泡具有其肿瘤归巢能力。这激发了我们设计MSC的EVs,使其充满化疗药物,并将其作为特洛伊木马直接输送到肿瘤细胞中。在我们的研究中,用吉西他滨(GCB)培养人牙髓间充质干细胞(DP-MSCs),这导致其被细胞吸收,并随后将药物分泌到EVs的条件培养基中。含有小EVs(潜在的外泌体)的浓缩条件培养基在体外显著抑制胰腺癌细胞系的细胞生长。DP-MSCs同时被工程化以表达自杀基因融合的酵母胞嘧啶二胺酶:尿嘧啶磷酸核糖基转移酶(yCD::UPRT)。自杀基因的产物在受体癌症细胞中将无毒前药5-氟胞嘧啶(5-FC)转化为高细胞毒性化疗药物5-氟尿嘧啶(5-FU)。5-FC转化为5-FU对癌症细胞的生长抑制有额外的作用。我们的研究结果表明,DP-MSC-EVs具有治疗潜力,可用于成功递送化疗药物,以及前药自杀基因治疗系统。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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