叶酸共轭牛血清白蛋白包被硒-ZIF-8 核/壳纳米粒子用于乳腺癌双靶点特异性给药。

IF 5.7 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Drug Delivery and Translational Research Pub Date : 2024-09-24 DOI:10.1007/s13346-024-01714-7
Arghavan Adibifar, Maryam Salimi, Neda Rostamkhani, Zahra Karami, Abdol-Hakim Agh-Atabay, Kobra Rostamizadeh
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引用次数: 0

摘要

甲氨蝶呤(MTX)是一种常用的化疗药物,但其水溶性有限,即使在局部注射时也会很快被清除。在本研究中,我们开发了叶酸共轭 BSA 稳定的硒-ZIF-8 核/壳纳米粒子,用于靶向递送 MTX 以抗击乳腺癌。FT-IR、XRD、SEM、TEM和元素图谱分析证实了FA-BSA@MTX@Se@ZIF-8的成功形成。所开发的纳米 DDS 的平均直径、多分散指数和 zeta 电位分别为 254.8 nm、0.17 和 - 16.5 mV。MTX从纳米载体中的释放行为与pH值有关,pH值为5.4时的累积释放率高于pH值为7.4时的释放率。BSA能明显改善纳米颗粒的血液相容性,在纳米颗粒表面添加BSA后,溶血率从12.67%降至5.12%。在 BSA@Se@ZIF-8 纳米颗粒中加入甲氨蝶呤后,其对 4T1 细胞的 IC50 值从 40.29 µg/mL 降至 16.54 µg/mL,而在其表面共轭叶酸后,该值甚至降至 12.27 µg/mL。对肿瘤小鼠体内抑制效果的评估表明,与游离 MTX 相比,FA-BSA@MTX@Se@ZIF-8 使肿瘤体积缩小了 2.8 倍,这归功于硒纳米粒子的抗癌效果、ZIF-8 的 pH 敏感性以及表面作为靶向剂的叶酸的存在。更重要的是,组织学研究和动物体重监测证实,所开发的纳米 DDS 没有明显的器官毒性。综上所述,在叶酸结合的 BSA 稳定硒-ZIF-8 纳米粒子中加入化疗药物可能会在未来的肿瘤治疗领域产生重大影响。
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Folic acid-conjugated bovine serum albumin-coated selenium-ZIF-8 core/shell nanoparticles for dual target-specific drug delivery in breast cancer.

Methotrexate (MTX), a frequently used chemotherapeutic agent, has limited water solubility, leading to rapid clearance even in local injections. In the present study, we developed folic acid-conjugated BSA-stabilized selenium-ZIF-8 core/shell nanoparticles for targeted delivery of MTX to combat breast cancer. FT-IR, XRD, SEM, TEM, and elemental mapping analysis confirmed the successful formation of FA-BSA@MTX@Se@ZIF-8. The developed nano-DDS had a mean diameter, polydispersity index, and zeta potential of 254.8 nm, 0.17, and - 16.5 mV, respectively. The release behavior of MTX from the nanocarriers was pH-dependent, where the cumulative release percentage at pH 5.4 was higher than at pH 7.4. BSA significantly improved the blood compatibility of nanoparticles so that after modifying their surface with BSA, the percentage of hemolysis decreased from 12.67 to 5.12%. The loading of methotrexate in BSA@Se@ZIF-8 nanoparticles reduced its IC50 on 4T1 cells from 40.29 µg/mL to 16.54 µg/mL, and by conjugating folic acid on the surface, this value even decreased to 12.27 µg/mL. In vivo evaluation of the inhibitory effect in tumor-bearing mice showed that FA-BSA@MTX@Se@ZIF-8 caused a 2.8-fold reduction in tumor volume compared to the free MTX, which is due to the anticancer effect of selenium nanoparticles, the pH sensitivity of ZIF-8, and the presence of folic acid on the surface as a targeting agent. More importantly, histological studies and animal body weight monitoring confirmed that developed nano-DDS does not have significant organ toxicity. Taking together, the incorporation of chemotherapeutics in folic acid-conjugated BSA-stabilized selenium-ZIF-8 nanoparticles may hold a significant impact in the field of future tumor management.

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来源期刊
Drug Delivery and Translational Research
Drug Delivery and Translational Research MEDICINE, RESEARCH & EXPERIMENTALPHARMACOL-PHARMACOLOGY & PHARMACY
CiteScore
11.70
自引率
1.90%
发文量
160
期刊介绍: The journal provides a unique forum for scientific publication of high-quality research that is exclusively focused on translational aspects of drug delivery. Rationally developed, effective delivery systems can potentially affect clinical outcome in different disease conditions. Research focused on the following areas of translational drug delivery research will be considered for publication in the journal. Designing and developing novel drug delivery systems, with a focus on their application to disease conditions; Preclinical and clinical data related to drug delivery systems; Drug distribution, pharmacokinetics, clearance, with drug delivery systems as compared to traditional dosing to demonstrate beneficial outcomes Short-term and long-term biocompatibility of drug delivery systems, host response; Biomaterials with growth factors for stem-cell differentiation in regenerative medicine and tissue engineering; Image-guided drug therapy, Nanomedicine; Devices for drug delivery and drug/device combination products. In addition to original full-length papers, communications, and reviews, the journal includes editorials, reports of future meetings, research highlights, and announcements pertaining to the activities of the Controlled Release Society.
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