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透明质酸包覆壳聚糖纳米粒作为辣根过氧化物酶/吲哚-3-乙酸前药复合物的载体:对膀胱癌细胞的表征和潜在治疗作用。

Hyaluronic acid-coated chitosan nanoparticles as carrier for the enzyme/prodrug complex based on horseradish peroxidase/indole-3-acetic acid: Characterization and potential therapeutic for bladder cancer cells.

机构信息

Tiradentes University, Av. Murilo Dantas 300, 49032-490, Aracaju, SE, Brazil; Institute of Technology and Research, Av. Murilo Dantas 300, 49032-490, Aracaju, SE, Brazil.

School of Technology, Pontifical Catholic University of Rio Grande do Sul - PUCRS, Av. Ipiranga 6681, 90619-900, Porto Alegre, RS, Brazil.

出版信息

Enzyme Microb Technol. 2021 Oct;150:109889. doi: 10.1016/j.enzmictec.2021.109889. Epub 2021 Aug 2.

Abstract

Hybrid nanoparticles composed of different biopolymers for delivery of enzyme/prodrug systems are of interest for cancer therapy. Hyaluronic acid-coated chitosan nanoparticles (CS/HA NP) were prepared to encapsulate individually an enzyme/pro-drug complex based on horseradish peroxidase (HRP) and indole-3-acetic acid (IAA). CS/HA NP showed size around 158 nm and increase to 170 and 200 nm after IAA and HRP encapsulation, respectively. Nanoparticles showed positive zeta potential values (between +20.36 mV and +24.40 mV) and higher encapsulation efficiencies for both nanoparticles (up to 90 %) were obtained. Electron microscopy indicated the formation of spherical particles with smooth surface characteristic. Physicochemical and thermal characterizations suggest the encapsulation of HRP and IAA. Kinetic parameters for encapsulated HRP were similar to those of the free enzyme. IAA-CS/HA NP showed a bimodal release profile of IAA with a high initial release (72 %) followed by a slow-release pattern. The combination of HRP-CS/HA NP and IAA- CS/HA NP reduced by 88 % the cell viability of human bladder carcinoma cell line (T24) in the concentrations 0.5 mM of pro-drug and 1.2 μg/mL of the enzyme after 24 h.

摘要

由不同生物聚合物组成的杂化纳米粒子,用于递送酶/前药系统,是癌症治疗的研究热点。壳聚糖-透明质酸纳米粒子(CS/HA NP)被制备为单独封装基于辣根过氧化物酶(HRP)和吲哚-3-乙酸(IAA)的酶/前药复合物。CS/HA NP 的粒径约为 158nm,在封装 IAA 和 HRP 后分别增加到 170nm 和 200nm。纳米粒子表现出正的zeta 电位值(介于+20.36mV 和+24.40mV 之间),并且两种纳米粒子的包封效率均较高(高达 90%)。电子显微镜表明形成了具有光滑表面特征的球形粒子。物理化学和热特性表明 HRP 和 IAA 的包封。包封 HRP 的动力学参数与游离酶相似。IAA-CS/HA NP 显示出 IAA 的双峰释放模式,初始释放(72%)较高,随后是缓慢释放模式。在浓度为 0.5mM 前药和 1.2μg/mL 酶时,HRP-CS/HA NP 和 IAA-CS/HA NP 的组合使人类膀胱癌细胞系(T24)的细胞活力降低了 88%,在 24 小时后。

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