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基于 2-硫代尿嘧啶功能化的金纳米粒子在乳腺癌细胞中的抗增殖和光热治疗作用。

Gold Nanoparticles Functionalized with 2-Thiouracil for Antiproliferative and Photothermal Therapies in Breast Cancer Cells.

机构信息

Department of Chemistry, University of Puerto Rico, Mayaguez Campus, Mayaguez, PR 00681, USA.

Department of Physical and Environmental Sciences, Texas A&M University-Corpus Christi, Corpus Christi, TX 78412, USA.

出版信息

Molecules. 2023 May 31;28(11):4453. doi: 10.3390/molecules28114453.

Abstract

Nanoparticles have been used to transport drugs to various body parts to treat cancer. Our interest is in gold nanoparticles (AuNPs) since they have the capacity to absorb light and convert it to heat, inducing cellular damage. This property is known as photothermal therapy (PTT) and has been studied in cancer treatment. In the present study, biocompatible citrate-reduced AuNPs were functionalized with a biologically active compound, 2-thiouracil (2-TU), of potential anticancer activity. Both the unfunctionalized (AuNPs) and functionalized (2-TU-AuNPs) were purified and characterized by UV-Vis absorption spectrophotometry, Zeta potential, and Transmission Electron Microscopy. Results showed monodispersed, spherical AuNPs with a mean core diameter of 20 ± 2 nm, a surface charge of -38 ± 5 mV, and a localized surface plasmon resonance peak at 520 nm. As a result of functionalization, the mean core diameter of 2-TU-AuNPs increased to 24 ± 4 nm, and the surface charge increased to -14 ± 1 mV. The functionalization of AuNPs and the load efficiency were further established through Raman spectroscopy and UV-Vis absorption spectrophotometry. The antiproliferative activities of AuNPs, 2-TU and 2-TU-AuNPs were examined by a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay in the MDA-MB-231 breast cancer cell line. It was established that AuNPs significantly enhanced the antiproliferative activity of 2-TU. Furthermore, the irradiation of the samples with visible light at 520 nm decreased the half-maximal inhibitory concentration by a factor of 2. Thus, the 2-TU drug concentration and its side effect during treatments could be significantly reduced by synergistically exploiting the antiproliferative activity of 2-TU loaded onto AuNPs and the PTT effect of AuNPs.

摘要

纳米粒子已被用于将药物输送到身体的各个部位以治疗癌症。我们对金纳米粒子(AuNPs)感兴趣,因为它们具有吸收光并将其转化为热量的能力,从而导致细胞损伤。这种特性称为光热疗法(PTT),并已在癌症治疗中进行了研究。在本研究中,生物相容的柠檬酸还原的 AuNPs 被功能化,即用具有潜在抗癌活性的生物活性化合物 2-硫代尿嘧啶(2-TU)进行功能化。未功能化的(AuNPs)和功能化的(2-TU-AuNPs)均通过紫外可见吸收分光光度法,Zeta 电位和透射电子显微镜进行纯化和表征。结果表明,AuNPs 呈单分散的球形,平均核心直径为 20±2nm,表面电荷为-38±5mV,局部表面等离子体共振峰位于 520nm。由于功能化,2-TU-AuNPs 的平均核心直径增加到 24±4nm,表面电荷增加到-14±1mV。通过拉曼光谱和紫外可见吸收分光光度法进一步证实了 AuNPs 的功能化和负载效率。通过 3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四氮唑溴化物(MTT)测定法在 MDA-MB-231 乳腺癌细胞系中检查了 AuNPs、2-TU 和 2-TU-AuNPs 的抗增殖活性。结果表明,AuNPs 显著增强了 2-TU 的抗增殖活性。此外,用 520nm 的可见光照射样品,使半最大抑制浓度降低了 2 倍。因此,通过协同利用负载在 AuNPs 上的 2-TU 的抗增殖活性和 AuNPs 的 PTT 效应,可以显著降低 2-TU 药物浓度及其在治疗中的副作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fec9/10254252/a6309cef1903/molecules-28-04453-g001.jpg

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