Wioletta Liwinska, Ewelina Waleka-Bagiel, Zbigniew Stojek, Marcin Karbarz, Ewelina Zabost
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A properly adjusted volume phase transition (VPT) temperature allowed independent shrinking of a) poly(ethylene glycol) methyl ether methacrylate (OEGMA) with di(ethylene glycol) and b) methyl ether methacrylate (MEO<sub>2</sub>MA) part of the network, and the exposition of hyaluronic acid methacrylate (MeHa) network based carboxylic groups for its targeted action with the cellular based receptors. This effect was substantial after raising temperature in typical hyperthermia-based treatment therapies. Additionally, novel tunable NGs gained an opportunity to store- and to efficient-enzyme-triggered release relatively low but highly therapeutic doses of doxorubicin (DOX) and mitoxantrone (MTX). The controlled enzymatic degradation of NGs could be enhanced by introducing more hyaluronidase enzyme (HAdase), that is usually overexpressed in cancer environments. MTT assay results revealed effective cytotoxic activity of the NGs against the human MCF-7 breast cancer cells, the A278 ovarian cancer cells and also cytocompatibility against the MCF-10A and HOF healthy cells. 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引用次数: 0
摘要
酶响应性聚合物基纳米结构是靶向给药载体关键材料的潜在候选材料。然而,其长期应用的主要风险在于短效聚合物结构的快速分解。另一个缺点是酶对位于网络内部的分子的可及性有限。在此,我们报告了一种含有混合网络的改良型环境响应和酶可裂解纳米凝胶载体。通过适当调节体积相变(VPT)温度,可使网络中的 a) 聚(乙二醇)甲基丙烯酸甲酯(OEGMA)与二(乙二醇)和 b) 甲基丙烯酸甲酯(MEO2MA)部分独立收缩,并使基于甲基丙烯酸透明质酸(MeHa)网络的羧基暴露出来,从而对细胞受体产生靶向作用。在典型的热疗疗法中,温度升高后,这种效果非常明显。此外,新型可调 NGs 还能储存并在酶触发下高效释放相对较低但治疗剂量较高的多柔比星(DOX)和米托蒽醌(MTX)。通过引入更多通常在癌症环境中过度表达的透明质酸酶(HAdase),可以增强 NGs 的可控酶降解。MTT 检测结果表明,NGs 对人类 MCF-7 乳腺癌细胞和 A278 卵巢癌细胞具有有效的细胞毒性活性,对 MCF-10A 和 HOF 健康细胞也具有细胞相容性。所获得的可调式混合网络导航管可作为一个有用的平台,用于治疗应用中其他药物和诊断的程序化传输。
Enzyme-triggered- and tumor-targeted delivery with tunable, methacrylated poly(ethylene glycols) and hyaluronic acid hybrid nanogels.
Enzyme-responsive polymeric-based nanostructures are potential candidates for serving as key materials in targeted drug delivery carriers. However, the major risk in their prolonged application is fast disassembling of the short-lived polymeric-based structures. Another disadvantage is the limited accessibility of the enzyme to the moieties that are located inside the network. Here, we report on a modified environmentally responsive and enzymatically cleavable nanogel carrier that contains a hybrid network. A properly adjusted volume phase transition (VPT) temperature allowed independent shrinking of a) poly(ethylene glycol) methyl ether methacrylate (OEGMA) with di(ethylene glycol) and b) methyl ether methacrylate (MEO2MA) part of the network, and the exposition of hyaluronic acid methacrylate (MeHa) network based carboxylic groups for its targeted action with the cellular based receptors. This effect was substantial after raising temperature in typical hyperthermia-based treatment therapies. Additionally, novel tunable NGs gained an opportunity to store- and to efficient-enzyme-triggered release relatively low but highly therapeutic doses of doxorubicin (DOX) and mitoxantrone (MTX). The controlled enzymatic degradation of NGs could be enhanced by introducing more hyaluronidase enzyme (HAdase), that is usually overexpressed in cancer environments. MTT assay results revealed effective cytotoxic activity of the NGs against the human MCF-7 breast cancer cells, the A278 ovarian cancer cells and also cytocompatibility against the MCF-10A and HOF healthy cells. The obtained tunable, hybrid network NGs might be used as a useful platform for programmed delivery of other pharmaceuticals and diagnostics in therapeutic applications.
期刊介绍:
Drug Delivery is an open access journal serving the academic and industrial communities with peer reviewed coverage of basic research, development, and application principles of drug delivery and targeting at molecular, cellular, and higher levels. Topics covered include all delivery systems including oral, pulmonary, nasal, parenteral and transdermal, and modes of entry such as controlled release systems; microcapsules, liposomes, vesicles, and macromolecular conjugates; antibody targeting; protein/peptide delivery; DNA, oligonucleotide and siRNA delivery. Papers on drug dosage forms and their optimization will not be considered unless they directly relate to the original drug delivery issues. Published articles present original research and critical reviews.