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甲氨蝶呤修饰的超顺磁性纳米粒子对大鼠乳腺肿瘤治疗效果及某些免疫因子的研究

Study on the therapeutic effect and some immune factors by methotrexate modified superparamagnetic nanoparticles in rat mammary tumors.

作者信息

Huang Li, Zhao Xing, Zhang Jun, Zhang Jiquan, Liao Weike, Fan Yanhua, Tang Jintian, He Zhixu, Gao Fuping, Ouyang Weiwei

机构信息

Department of Thoracic Oncology, The Affiliated Hospital of Guizhou Medical University and the Affiliated of Cancer Hospital of Guizhou Medical University Guiyang 550004 China

Stem Cell and Tissue Engineering Research Center, Guizhou Medical University Guiyang 550004 China.

出版信息

Nanoscale Adv. 2024 Nov 26;7(2):601-613. doi: 10.1039/d4na00295d. eCollection 2025 Jan 14.

Abstract

: this study investigates the efficacy, immunological impact, and preliminary safety of methotrexate (MTX) modified magnetic FeO nanoparticles in thermochemotherapy for mammary tumors in rats. : transmission electron microscopy images revealed that the MTX-modified magnetic FeO nanoparticles are nearly spherical, approximately 10 nm in diameter. Chemically co-precipitated PEI-modified magnetic nanoparticles were utilized for thermotherapy, while MTX-modified nanoparticles were employed for thermochemotherapy. These nanoparticles were locally injected into the Walker-256 tumor tissues of Wistar rats. The experimental design included twelve groups, encompassing various protocols of thermotherapy and thermochemotherapy at 47 °C and 42 °C, a group receiving only MTX nanoparticle chemotherapy, and several control groups. The biodistribution of residual magnetic nanoparticles was assessed in vital organs such as the heart, liver, lungs, kidneys, and brain. : demonstrated that these magnetic nanoparticles primarily accumulated in the tumor's central region and were unevenly distributed at the margins. The nanoparticles were capable of penetrating tumor cells but were more dispersed around them. Importantly, no residual magnetic nanoparticles were detected in vital organs. Significant tumor reduction and prolonged survival times were observed in the 47 °C thermochemotherapy group, the 47 °C thermotherapy group and the repeated 42 °C thermochemotherapy group. Additionally, significant increases in IL-2 and IFN-γ levels, along with a decrease in IL-4 levels, were detected in the 47 °C thermochemotherapy and 47 °C thermotherapy groups. : MTX-modified FeO magnetic nanoparticles demonstrate potential as an effective medium for thermochemotherapy. They are safe, tolerable, contribute to prolonged survival, and enhance immune functions in tumor-bearing rats without leaving residues in vital organs. These results provide a promising foundation for future cancer treatment research.

摘要

本研究调查了甲氨蝶呤(MTX)修饰的磁性FeO纳米颗粒在大鼠乳腺肿瘤热化疗中的疗效、免疫影响和初步安全性。透射电子显微镜图像显示,MTX修饰的磁性FeO纳米颗粒近乎球形,直径约为10纳米。化学共沉淀的PEI修饰磁性纳米颗粒用于热疗,而MTX修饰的纳米颗粒用于热化疗。这些纳米颗粒被局部注射到Wistar大鼠的Walker-256肿瘤组织中。实验设计包括十二组,涵盖了在47℃和42℃下的各种热疗和热化疗方案、一组仅接受MTX纳米颗粒化疗以及几个对照组。在心脏、肝脏、肺、肾脏和大脑等重要器官中评估了残留磁性纳米颗粒的生物分布。结果表明,这些磁性纳米颗粒主要积聚在肿瘤的中心区域,边缘分布不均匀。纳米颗粒能够穿透肿瘤细胞,但在其周围分布更分散。重要的是,在重要器官中未检测到残留磁性纳米颗粒。在47℃热化疗组、47℃热疗组和重复42℃热化疗组中观察到显著的肿瘤缩小和延长的生存时间。此外,在47℃热化疗组和47℃热疗组中检测到IL-2和IFN-γ水平显著升高,同时IL-水平降低。MTX修饰的FeO磁性纳米颗粒显示出作为热化疗有效介质的潜力。它们安全、可耐受,有助于延长生存期,并增强荷瘤大鼠的免疫功能,且不会在重要器官中留下残留物。这些结果为未来癌症治疗研究提供了有希望的基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0451/11730341/8de51283bc37/d4na00295d-f1.jpg

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