RES-CMCNPs可增强EAC小鼠的抗氧化性、促炎性以及肿瘤实体对γ-照射的敏感性。

Q2 Pharmacology, Toxicology and Pharmaceutics

Pharmaceutical nanotechnology Pub Date : 2024-04-09 DOI:10.2174/0122117385290497240324190453

Mohamed S Mansour, Amira A Mahmoud, Mohannad A Sayah, Zahraa N Mohamed, Mohammed A Hussein, Diana A ALsherif

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The radiosensitizing properties of RES-CMCNPs were also evaluated in vitro and in vivo against EAC-carrying rodents. The LD50 of Res-CMCNPs was estimated and its 1/20 LD50 was prepared for treating EAC transplanted mice. Results: The results revealed that the Res-CMCNPs exhibited a high entrapment efficiency (85.46%) and a size of approximately 184.60 ±17.36 nm with zeta potential value equals -51.866 mv. Also, the UV spectra of Res and Res-CMCNPs have strong absorption at 230 and 250 nm. The percentage of resveratrol release at pHs 5.8 and 7.4 was found to be 56.73% and 51.60 %, respectively, after 24 h at 100 rpm. Also, the FTIR analysis confirmed the chemical stability of resveratrol in Res-CMCNPs cross-linking. The IC50 values of Res-CMCNPs against EAC cells viability were 32.99, 25.46, and 22.21 µg after 24-, 48- and 72 h incubation, respectively, whereas those of ResCMCNPs in combination with γ-irradiation after 6-, 10 and 12-mins exposure were 24.07, 16.06 and 7.48 µg, respectively. Also, the LD50 of Res-CMCNPs was 2180 mg/kg.b.w. The treatment of EAC-bearing mice with Res-CMCNPs plus γ-irradiation improved plasma levels of NO, caspase-3, P53 and NF-kB levels as well as liver MDA, GSH, SOD, CAT, LT-B4, aromatase, Bax, Bcl2 and TGF-β levels and exhibited more significant anticancer activity than administration of ResCMCNPs and/or exposure to γ-irradiation individually. On the other hand, administration of ResCMCNPs in combination with γ-irradiation attenuated liver mRNAs (21, 29b, 181a, and 451) gene expression. 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引用次数: 0

摘要

目的：白藜芦醇（Res）是一种存在于葡萄和桑葚等多种植物中的双功能化合物。纳米技术在医学领域有着广阔的应用前景。多篇手稿报道了各种纳米材料作为肿瘤细胞放射增敏剂的能力。本研究旨在评估 Res-CMCNPs 对 EAC 小鼠的抗肿瘤和放射增敏作用。研究方法采用 CMC 乳化交联技术开发了 Res-CMCNPs。对 RES-CMCNPs 的包封效率（%）、粒度、多分散指数和 ZETA 电位、紫外光谱、傅立叶变换红外光谱以及药物释放进行了评估和描述。此外，还评估了 RES-CMCNPs 在体外和体内对携带 EAC 的啮齿动物的辐射敏感性。估算了 RES-CMCNPs 的半数致死剂量（LD50），并将其 1/20 LD50 用于治疗 EAC 移植小鼠。结果显示结果表明，Res-CMCNPs 的包封效率高（85.46%），尺寸约为 184.60 ±17.36 nm，zeta 电位值等于 -51.866 mv。此外，Res 和 Res-CMCNPs 的紫外光谱在 230 纳米和 250 纳米处有很强的吸收。在 pH 值为 5.8 和 7.4 的条件下，100 转/分条件下 24 小时后，白藜芦醇的释放率分别为 56.73% 和 51.60%。傅立叶变换红外光谱分析也证实了白藜芦醇在 Res-CMCNPs 交联过程中的化学稳定性。在培养 24、48 和 72 小时后，Res-CMCNPs 对 EAC 细胞活力的 IC50 值分别为 32.99、25.46 和 22.21 µg，而 ResCMCNPs 与γ-辐照结合后，在照射 6、10 和 12 分钟后的 IC50 值分别为 24.07、16.06 和 7.48 µg。此外，Res-CMCNPs 的半数致死剂量为 2180 mg/kg.b.w.。用 Res-CMCNPs 和 γ-irradiation 处理 EAC 小鼠，可改善血浆中 NO、caspase-3、P53 和 NF-kB 的水平，以及肝脏中 MDA、GSH、SOD、CAT、LT-B4、芳香化酶、Bax、Bcl2 和 TGF-β 的水平，与单独施用 ResCMCNPs 和/或暴露于 γ-irradiation 相比，具有更显著的抗癌活性。另一方面，ResCMCNPs 与 γ 辐射结合使用可减轻肝脏 mRNAs（21、29b、181a 和 451）基因的表达。结论将白藜芦醇接枝到羧甲基壳聚糖上似乎是一种很有前景的癌症治疗策略，可通过改善促炎特征和抗氧化生物标志物的水平，增强肿瘤细胞对辐射的敏感性。

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RES-CMCNPs Enhance Antioxidant, Proinflammatory, and Sensitivity of Tumor Solids to γ-Irradiation in EAC-Bearing Mice.

Objectives: Resveratrol (Res) is a bifunctional compound found in numerous plants, including grapes and mulberries. Nanotechnology has promising applications in medicine. The ability of various nanomaterials to serve as radiosensitizers against tumor cells were reported in several manuscripts. The present investigation aimed to assess the antitumor and radiosensitizing effects of Res-CMCNPs on EAC-bearing mice.

Methods: Res-CMCNPs have been developed using the CMC emulsification cross-linking technique. Entrapment efficiency (%), particle size, Polydispersity index and ZETA potential, UV, FTIR spectra, and drug release were evaluated and described for RES-CMCNPs. The radiosensitizing properties of RES-CMCNPs were also evaluated in vitro and in vivo against EAC-carrying rodents. The LD50 of Res-CMCNPs was estimated and its 1/20 LD50 was prepared for treating EAC transplanted mice.

Results: The results revealed that the Res-CMCNPs exhibited a high entrapment efficiency (85.46%) and a size of approximately 184.60 ±17.36 nm with zeta potential value equals -51.866 mv. Also, the UV spectra of Res and Res-CMCNPs have strong absorption at 230 and 250 nm. The percentage of resveratrol release at pHs 5.8 and 7.4 was found to be 56.73% and 51.60 %, respectively, after 24 h at 100 rpm. Also, the FTIR analysis confirmed the chemical stability of resveratrol in Res-CMCNPs cross-linking. The IC50 values of Res-CMCNPs against EAC cells viability were 32.99, 25.46, and 22.21 µg after 24-, 48- and 72 h incubation, respectively, whereas those of ResCMCNPs in combination with γ-irradiation after 6-, 10 and 12-mins exposure were 24.07, 16.06 and 7.48 µg, respectively. Also, the LD50 of Res-CMCNPs was 2180 mg/kg.b.w. The treatment of EAC-bearing mice with Res-CMCNPs plus γ-irradiation improved plasma levels of NO, caspase-3, P53 and NF-kB levels as well as liver MDA, GSH, SOD, CAT, LT-B4, aromatase, Bax, Bcl2 and TGF-β levels and exhibited more significant anticancer activity than administration of ResCMCNPs and/or exposure to γ-irradiation individually. On the other hand, administration of ResCMCNPs in combination with γ-irradiation attenuated liver mRNAs (21, 29b, 181a, and 451) gene expression.

Conclusion: Grafting resveratrol onto carboxymethyl chitosan appears to be a promising strategy for cancer therapy as a radiosensitizer by potentiating tumor cells' sensitivity to radiation by improving levels of proinflammatory features and antioxidant biomarkers.

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来源期刊

Pharmaceutical nanotechnology Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science

CiteScore

4.20

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0.00%

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期刊介绍： Pharmaceutical Nanotechnology publishes original manuscripts, full-length/mini reviews, thematic issues, rapid technical notes and commentaries that provide insights into the synthesis, characterisation and pharmaceutical (or diagnostic) application of materials at the nanoscale. The nanoscale is defined as a size range of below 1 µm. Scientific findings related to micro and macro systems with functionality residing within features defined at the nanoscale are also within the scope of the journal. Manuscripts detailing the synthesis, exhaustive characterisation, biological evaluation, clinical testing and/ or toxicological assessment of nanomaterials are of particular interest to the journal’s readership. Articles should be self contained, centred around a well founded hypothesis and should aim to showcase the pharmaceutical/ diagnostic implications of the nanotechnology approach. Manuscripts should aim, wherever possible, to demonstrate the in vivo impact of any nanotechnological intervention. As reducing a material to the nanoscale is capable of fundamentally altering the material’s properties, the journal’s readership is particularly interested in new characterisation techniques and the advanced properties that originate from this size reduction. Both bottom up and top down approaches to the realisation of nanomaterials lie within the scope of the journal.