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pH 响应性载白藜芦醇 ZIF-8 纳米粒子用单宁酸修饰用于促进结肠癌细胞凋亡。

pH-responsive resveratrol-loaded ZIF-8 nanoparticles modified with tannic acid for promoting colon cancer cell apoptosis.

机构信息

The First Hospital of Lanzhou University, Lanzhou, China.

The First Clinical Medical College of Lanzhou University, Lanzhou, China.

出版信息

J Biomed Mater Res B Appl Biomater. 2024 Jan;112(1):e35320. doi: 10.1002/jbm.b.35320. Epub 2023 Sep 13.

DOI:10.1002/jbm.b.35320
PMID:37702969
Abstract

Resveratrol (Res) is known for its potential in treating various types of cancers, with a particular advantage of causing minimal toxic side effects. However, its clinical application is constrained by challenges such as poor bioavailability, low water solubility, and chemical instability in neutral and alkaline environments. In light of these limitations, we have developed a pH-responsive drug delivery nanoplatform, Res@ZIF-8/TA NPs, which exhibits good biocompatibility and shows promise for in vitro cancer therapy. Benefiting from the mild reaction conditions provided by zeolitic imidazolate frameworks (ZIFs), a "one-pot method" was used for drug synthesis and loading, resulting in a satisfactory loading capacity. Notably, Res@ZIF-8/TA NPs respond to acidic environments, leading to an improved drug release profile with a controlled release effect. Our cell-based experiments indicated that tannic acid (TA) modification enhances the biocompatibility of ZIFs. 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide (MTT assay), Hoechst 33342/PI staining, cell scratch assay, Transwell and Reverse Transcription quantitative PCR (RT-qPCR) assays further demonstrated that Res@ZIF-8/TA NPs inhibited colon cancer cell migration and invasion, and promoted apoptosis of colon cancer cells, suggesting a therapeutic potential and demonstrating anti-cancer properties. In conclusion, the Res@ZIF-8/TA NPs pH-responsive drug delivery systems we developed may offer a promising avenue for cancer therapy. By addressing some of the challenges associated with Res-based treatments, this system could contribute to advancements in cancer therapeutics.

摘要

白藜芦醇(Res)因其治疗各种类型癌症的潜力而备受关注,尤其具有引起最小毒性副作用的优点。然而,其临床应用受到生物利用度差、水溶性低以及在中性和碱性环境中化学不稳定等挑战的限制。有鉴于此,我们开发了一种 pH 响应型药物传递纳米平台,Res@ZIF-8/TA NPs,该平台具有良好的生物相容性,有望用于体外癌症治疗。受益于沸石咪唑酯骨架(ZIFs)提供的温和反应条件,采用“一锅法”进行药物合成和负载,实现了令人满意的载药能力。值得注意的是,Res@ZIF-8/TA NPs 对酸性环境作出响应,导致药物释放特性得到改善,具有控制释放效果。我们的细胞实验表明,单宁酸(TA)修饰增强了 ZIFs 的生物相容性。基于细胞的实验,包括 3-(4,5)-二甲基噻唑 (-z-y1)-3,5-二苯基四氮唑溴盐(MTT 测定)、Hoechst 33342/PI 染色、细胞划痕实验、Transwell 和逆转录定量聚合酶链式反应(RT-qPCR)实验进一步表明,Res@ZIF-8/TA NPs 抑制结肠癌细胞迁移和侵袭,并促进结肠癌细胞凋亡,提示其具有治疗潜力和抗癌特性。总之,我们开发的 Res@ZIF-8/TA NPs pH 响应型药物传递系统可能为癌症治疗提供了一种有前途的途径。通过解决基于 Res 的治疗方法所面临的一些挑战,该系统可能有助于癌症治疗的进展。

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