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通过共包封白藜芦醇和纤维素酶合成的用于生物医学应用的ZIF-8纳米载体。

ZIF-8 nanocarriers synthesized by co-encapsulating resveratrol and cellulase for biomedical applications.

作者信息

Sheik Aliya, Rethinasabapathy Muruganantham, Kodiveri Muthukaliannan Gothandam, Safarkhani Moein, Kang Haneul, Kim Donghyeon, Alhammadi Munirah, Jung Erica, Huh Yun Suk

机构信息

NanoBio High-Tech Materials Research Center, Department of Biological Sciences and Engineering, Inha University, 100 Inha-ro, Incheon 22212, Republic of Korea.

School of BioSciences and Technology, Vellore Institute of Technology, Vellore 632014, Tamil Nadu, India.

出版信息

Int J Biol Macromol. 2024 Dec;283(Pt 4):137756. doi: 10.1016/j.ijbiomac.2024.137756. Epub 2024 Nov 16.

Abstract

Drug conjugation with enzymes is one of the innovative antibacterial nanocarriers used as a delivery system for cancer therapy. Zeolitic imidazolate framework-8 (ZIF-8) was synthesized, dual encapsulated with cellulase (CL) enzyme, and resveratrol (Resv) drug formed ZIF-8@CL&Resv. Cellulase and resveratrol hydrophobic nature have bound them together and imparted a negative charge on the ZIF-8, resulting in the decrease of zeta potential from 22.7 mV (ZIF-8) to 3.82 mV (ZIF-8@CL&Resv). The cellulase like a scaffold regulated the pH-responsive release of resveratrol enhancing its bioavailability. Molecular docking studies provided evidence of the major interaction between the biofilm-related proteins with cellulase and resveratrol. The encapsulated cellulase showed high enzymatic activity and possibly exhibited antibacterial effects by dissolving the biofilm and exposing bacteria to resveratrol action. Resveratrol released sustainably exhibited significant antioxidant and antibacterial activity against selected bacterial species. ZIF-8@CL&Resv exhibited high biocompatibility and had a potent cytotoxic effect against triple-negative breast cancer cells MDA MB 231 with an IC-value of 17.18 μg/mL compared to ZIF-8 control with 90.47 μg/mL. ZIF-8@CL&Resv treatment led to 61.81 % cell death, apoptosis induction, increased ROS generation, and decreased mitochondrial membrane potential. Overall, data demonstrated that ZIF-8@CL&Resv is a novel drug release system and a potential catalytic nanoparticle for antimicrobial and anticancer applications.

摘要

药物与酶的缀合是用作癌症治疗递送系统的创新抗菌纳米载体之一。合成了沸石咪唑酯骨架-8(ZIF-8),用纤维素酶(CL)酶进行双重包封,白藜芦醇(Resv)药物形成ZIF-8@CL&Resv。纤维素酶和白藜芦醇的疏水性质将它们结合在一起,并使ZIF-8带上负电荷,导致zeta电位从22.7 mV(ZIF-8)降至3.82 mV(ZIF-8@CL&Resv)。纤维素酶像一个支架一样调节白藜芦醇的pH响应释放,提高其生物利用度。分子对接研究提供了生物膜相关蛋白与纤维素酶和白藜芦醇之间主要相互作用的证据。包封的纤维素酶显示出高酶活性,并可能通过溶解生物膜并使细菌暴露于白藜芦醇的作用而表现出抗菌效果。可持续释放的白藜芦醇对选定的细菌物种表现出显著的抗氧化和抗菌活性。ZIF-8@CL&Resv表现出高生物相容性,对三阴性乳腺癌细胞MDA MB 231具有强大的细胞毒性作用,IC值为17.18 μg/mL,而ZIF-8对照的IC值为90.47 μg/mL。ZIF-8@CL&Resv处理导致61.81%的细胞死亡、凋亡诱导、活性氧生成增加和线粒体膜电位降低。总体而言,数据表明ZIF-8@CL&Resv是一种新型药物释放系统,也是一种用于抗菌和抗癌应用的潜在催化纳米颗粒。

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