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Gold Nanoparticles Functionalized with Au–Se-Bonded Peptides Used as Gatekeepers for the Off-Target Release of Resveratrol in the Treatment of Triple-Negative Breast Cancer
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2023-01-03 , DOI: 10.1021/acsami.2c10221
Xiaojun Liu 1 , Jiahao Liu 1 , Shushen Xu 1 , Xiaofeng Li 1 , Zhonghui Wang 1 , Xiaonan Gao 1 , Bo Tang 1 , Kehua Xu 1
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2023-01-03 , DOI: 10.1021/acsami.2c10221
Xiaojun Liu 1 , Jiahao Liu 1 , Shushen Xu 1 , Xiaofeng Li 1 , Zhonghui Wang 1 , Xiaonan Gao 1 , Bo Tang 1 , Kehua Xu 1
Affiliation
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Resveratrol has been garnering considerable attention as a promising chemopreventive and chemotherapeutic drug against metastatic tumors such as triple-negative breast cancer (TNBC). However, the potential in vivo application of resveratrol has been highly limited due to its poor solubility, rapid conjugation, low bioavailability, and bioactivity. In this study, a silica mesoporous nanoparticle (MSN)-based drug delivery system (DDS), named Au–Se@MSN, is developed to deliver the loaded resveratrol, endowing it with properties of targeted delivery, excellent bioavailability, and antioxidation of resveratrol. In Au–Se@MSN(RES), gold nanoparticles functionalized with selenol-modified uPA-specific peptides act as gatekeepers to avoid the interference of glutathione in the bloodstream and realize negligible premature release of resveratrol during delivery. Au–Se@MSN(RES) shows prolonged resveratrol release at the tumor site and endows resveratrol with a remarkable in vitro therapeutic effect. The pharmacological dose of resveratrol treatment on MDA-MB-231 cells was found to result in the generation of a high level of NAD(P)H other than H2O2, indicating reductive stress instead of oxidative stress involved in the resveratrol therapeutic process. In vivo experiments showed that Au–Se@MSN greatly improves the chemotherapeutic effect of resveratrol on mice bearing TNBC tumors, and damage to normal tissues and cells is negligible. Overall, Au–Se@MSN is a potential tool for further studies on the anticancer mechanism and clinical applications of resveratrol.
中文翻译：
用金硒键合肽功能化的金纳米粒子用作三阴性乳腺癌治疗中白藜芦醇脱靶释放的看门人
白藜芦醇作为一种很有前途的化学预防和化学治疗药物，对转移性肿瘤如三阴性乳腺癌 (TNBC) 已引起广泛关注。然而，潜在的体内白藜芦醇由于溶解性差、偶联速度快、生物利用度低、生物活性低等特点，其应用受到很大限制。在这项研究中，开发了一种名为 Au–Se@MSN 的基于二氧化硅介孔纳米粒子 (MSN) 的药物递送系统 (DDS) 来递送负载的白藜芦醇，赋予其靶向递送、优异的生物利用度和白藜芦醇的抗氧化特性. 在 Au–Se@MSN(RES) 中，用硒醇修饰的 uPA 特异性肽功能化的金纳米粒子充当看门人，避免谷胱甘肽在血液中的干扰，并在输送过程中实现可忽略的白藜芦醇过早释放。Au–Se@MSN(RES) 显示白藜芦醇在肿瘤部位的释放时间延长，并赋予白藜芦醇显着的体外治疗效果。发现白藜芦醇对 MDA-MB-231 细胞的药理学剂量处理导致产生高水平的 NAD(P)H 而不是 H 2 O 2，表明白藜芦醇治疗过程中涉及还原应激而不是氧化应激. 体内实验表明，Au-Se@MSN大大提高了白藜芦醇对荷瘤小鼠的化疗作用，而对正常组织和细胞的损伤可以忽略不计。总体而言，Au–Se@MSN 是进一步研究白藜芦醇抗癌机制和临床应用的潜在工具。
更新日期：2023-01-03
中文翻译：
用金硒键合肽功能化的金纳米粒子用作三阴性乳腺癌治疗中白藜芦醇脱靶释放的看门人
白藜芦醇作为一种很有前途的化学预防和化学治疗药物，对转移性肿瘤如三阴性乳腺癌 (TNBC) 已引起广泛关注。然而，潜在的体内白藜芦醇由于溶解性差、偶联速度快、生物利用度低、生物活性低等特点，其应用受到很大限制。在这项研究中，开发了一种名为 Au–Se@MSN 的基于二氧化硅介孔纳米粒子 (MSN) 的药物递送系统 (DDS) 来递送负载的白藜芦醇，赋予其靶向递送、优异的生物利用度和白藜芦醇的抗氧化特性. 在 Au–Se@MSN(RES) 中，用硒醇修饰的 uPA 特异性肽功能化的金纳米粒子充当看门人，避免谷胱甘肽在血液中的干扰，并在输送过程中实现可忽略的白藜芦醇过早释放。Au–Se@MSN(RES) 显示白藜芦醇在肿瘤部位的释放时间延长，并赋予白藜芦醇显着的体外治疗效果。发现白藜芦醇对 MDA-MB-231 细胞的药理学剂量处理导致产生高水平的 NAD(P)H 而不是 H 2 O 2，表明白藜芦醇治疗过程中涉及还原应激而不是氧化应激. 体内实验表明，Au-Se@MSN大大提高了白藜芦醇对荷瘤小鼠的化疗作用，而对正常组织和细胞的损伤可以忽略不计。总体而言，Au–Se@MSN 是进一步研究白藜芦醇抗癌机制和临床应用的潜在工具。
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