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载甲氨蝶呤的多壳层金纳米粒子：一种新型纳米治疗方法，可提高抗肿瘤和抗氧化活性，增强生物相容性。

Multi-shell gold nanoparticles functionalized with methotrexate: a novel nanotherapeutic approach for improved antitumoral and antioxidant activity and enhanced biocompatibility.

机构信息

Centre of Advanced Research in Bionanoconjugates and Biopolymers, "Petru Poni" Institute of Macromolecular Chemistry, Iasi, Romania.

Department of Microbiology and Immunology, Research Institute of the University of Bucharest-ICUB, Bucharest, Romania.

出版信息

Drug Deliv. 2024 Dec;31(1):2388624. doi: 10.1080/10717544.2024.2388624. Epub 2024 Aug 17.

DOI:10.1080/10717544.2024.2388624
PMID:39152905
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11332291/
Abstract

Methotrexate (MTX) is a folic acid antagonist routinely used in cancer treatment, characterized by poor water solubility and low skin permeability. These issues could be mitigated by using drug delivery systems, such as functionalized gold nanoparticles (AuNPs), known for their versatility and unique properties. This study aimed to develop multi-shell AuNPs functionalized with MTX for the improvement of MTX antitumoral, antioxidant, and biocompatibility features. Stable phosphine-coated AuNPs were synthesized and functionalized with tailored polyethylene glycol (PEG) and short-branched polyethyleneimine (PEI) moieties, followed by MTX covalent binding. Physicochemical characterization by UV-vis and Fourier-transform infrared spectroscopy (FTIR) spectroscopy, dynamic light scattering (DLS), scanning transmission electron microscopy (STEM), and X-ray photoelectron spectroscopy (XPS) confirmed the synthesis at each step. The antioxidant activity of functionalized AuNPs was determined using DPPH radical scavenging assay, ferric ions' reducing antioxidant power (FRAP), and cupric reducing antioxidant capacity (CUPRAC) assays. Biocompatibility and cytotoxicity were assessed using MTT and LDH assays on HaCaT human keratinocytes and CAL27 squamous cell carcinoma. MTX functionalized AuNPs demonstrated enhanced antioxidant activity and a pronounced cytotoxic effect on the tumoral cells compared to their individual components, highlighting their potential for improving cancer therapy.

摘要

甲氨蝶呤（MTX）是一种常用于癌症治疗的叶酸拮抗剂，其水溶性差，皮肤渗透性低。这些问题可以通过使用药物传递系统来缓解，例如功能化金纳米粒子（AuNPs），其具有多功能性和独特的性质。本研究旨在开发多壳层 MTX 功能化的 AuNPs，以改善 MTX 的抗肿瘤、抗氧化和生物相容性特征。合成了稳定的膦涂层 AuNPs，并对其进行了定制的聚乙二醇（PEG）和短支化聚乙烯亚胺（PEI）部分的功能化，然后进行 MTX 共价结合。通过紫外-可见分光光度法和傅里叶变换红外光谱（FTIR）光谱、动态光散射（DLS）、扫描透射电子显微镜（STEM）和 X 射线光电子能谱（XPS）对物理化学性质进行了表征，证实了每一步的合成。通过 DPPH 自由基清除测定法、铁离子还原抗氧化能力（FRAP）和铜还原抗氧化能力（CUPRAC）测定法测定了功能化 AuNPs 的抗氧化活性。通过 MTT 和 LDH 测定法在 HaCaT 人角质形成细胞和 CAL27 鳞状细胞癌细胞上评估了生物相容性和细胞毒性。与各自的成分相比，MTX 功能化的 AuNPs 表现出增强的抗氧化活性和对肿瘤细胞的显著细胞毒性作用，突出了它们在改善癌症治疗方面的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eba0/11332291/4d24ca9a21e2/IDRD_A_2388624_F0010_C.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eba0/11332291/3fee7b2f4d98/IDRD_A_2388624_SCH0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eba0/11332291/6321e211e49a/IDRD_A_2388624_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eba0/11332291/612bd9fc583f/IDRD_A_2388624_F0002_C.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eba0/11332291/e2aa093ebe1d/IDRD_A_2388624_F0007_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eba0/11332291/891e38692e27/IDRD_A_2388624_F0008_C.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eba0/11332291/4d24ca9a21e2/IDRD_A_2388624_F0010_C.jpg

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