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用于选择性增强X射线诱导光动力疗法的新型黄素单核苷酸功能化氟化铈纳米颗粒

Novel Flavin Mononucleotide-Functionalized Cerium Fluoride Nanoparticles for Selective Enhanced X-Ray-Induced Photodynamic Therapy.

作者信息

Kornienko Anastasia I, Teplonogova Maria A, Shevelyova Marina P, Popkov Matvei A, Popov Anton L, Ivanov Vladimir E, Popova Nelli R

机构信息

Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino 142290, Russia.

Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences, Moscow 119334, Russia.

出版信息

J Funct Biomater. 2024 Dec 10;15(12):373. doi: 10.3390/jfb15120373.

Abstract

X-ray-induced photodynamic therapy (X-PDT) represents a promising new method of cancer treatment. A novel type of nanoscintillator based on cerium fluoride (CeF) nanoparticles (NPs) modified with flavin mononucleotide (FMN) has been proposed. A method for synthesizing CeF-FMN NPs has been developed, enabling the production of colloidal, spherical NPs with an approximate diameter of 100 nm, low polydispersity, and a high fluorescence quantum yield of 0.42. It has been demonstrated that CeF-FMN NPs exhibit pH-dependent radiation-induced redox activity when exposed to X-rays. This activity results in the generation of reactive oxygen species, which is associated with the scintillation properties of cerium and the transfer of electrons to FMN. The synthesized NPs have been demonstrated to exhibit minimal cytotoxicity towards normal cells (NCTC L929 fibroblasts) but are more toxic to tumor cells (epidermoid carcinoma A431). Concurrently, the synthesized NPs (CeF and CeF-FMN NPs) demonstrate a pronounced selective radiosensitizing effect on tumor cells at concentrations of 10 and 10 M, resulting in a significant reduction in their clonogenic activity, increasing radiosensitivity for cancer cells by 1.9 times following X-ray irradiation at a dose of 3 to 6 Gy. In the context of normal cells, these nanoparticles serve the function of antioxidants, maintaining a high level of clonogenic activity. Functional nanoscintillators on the basis of cerium fluoride can be used as part of the latest technologies for the treatment of tumors within the framework of X-PDT.

摘要

X射线诱导光动力疗法(X-PDT)是一种很有前景的新型癌症治疗方法。人们提出了一种基于用黄素单核苷酸(FMN)修饰的氟化铈(CeF)纳米颗粒(NPs)的新型纳米闪烁体。已经开发出一种合成CeF-FMN NPs的方法,能够生产出近似直径为100 nm的胶体球形NPs,具有低多分散性和0.42的高荧光量子产率。已经证明,CeF-FMN NPs在暴露于X射线时表现出pH依赖性辐射诱导的氧化还原活性。这种活性导致活性氧的产生,这与铈的闪烁特性以及电子向FMN的转移有关。已证明合成的NPs对正常细胞(NCTC L929成纤维细胞)表现出最小的细胞毒性,但对肿瘤细胞(表皮样癌A431)毒性更大。同时,合成的NPs(CeF和CeF-FMN NPs)在浓度为10和10 M时对肿瘤细胞表现出明显的选择性放射增敏作用,导致其克隆形成活性显著降低,在3至6 Gy的X射线照射后,癌细胞的放射敏感性提高了1.9倍。在正常细胞的情况下,这些纳米颗粒起到抗氧化剂的作用,维持高水平的克隆形成活性。基于氟化铈的功能性纳米闪烁体可作为X-PDT框架内最新肿瘤治疗技术的一部分使用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e4b/11676406/31cb86b1d7d0/jfb-15-00373-g001.jpg

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