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贝伐单抗偶联姜黄素纳米颗粒在体外促进人恶性口腔角质形成细胞的细胞毒性和凋亡。

Bevacizumab-Conjugated Curcumin Nanoparticles Promote Cytotoxicity and Apoptosis in Human Malignant Oral Keratinocytes In Vitro.

作者信息

Senthil Rethinam

机构信息

Associate Professor, Department of Pharmacology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, Chennai, Tamilnadu, India.

出版信息

J Oral Maxillofac Surg. 2025 May 27. doi: 10.1016/j.joms.2025.05.014.

DOI:10.1016/j.joms.2025.05.014
PMID:40514017
Abstract

BACKGROUND

Targeted, biologically-based therapeutic agents seek to reduce tumor burden and treatment side effects. Curcumin nanoparticle (CuNP)-based drug delivery systems conjugated have been shown to target and inhibit the growth of human malignant oral keratinocytes in vitro.

PURPOSE

The purpose of this study was to conjugate physiologically clotted fibrin (PCF) and CuNPs with bevacizumab (BVZ), characterize the newly formed nanoparticles, and test their growth inhibition on human oral cancer cells in vitro.

STUDY DESIGN, SETTING, SAMPLE: This in-vitro study was conducted at the White Lab, Cell Culture Laboratory, Saveetha; Dental College and Hospitals, Chennai, from June 2 to August 20, 2024. The human malignant oral keratinocyte cell line UM-SCC-1 was used.

PREDICTOR VARIABLES

The primary predictor variable was BVZ in the BVZ: PCF: CuNP nanoparticle formulation. The control consisted of PCF: CuNP nanoparticles.

MAIN OUTCOME VARIABLES

The outcome variables were the successful synthesis of BVZ: PCF: CuNP and growth inhibition of UM-SCC-1 cells. The synthesized nanoparticles were characterized using ultraviolet, fourier-transform infrared, and high-resolution scanning electron microscopy. In vitro cytotoxicity, apoptosis, and scratch wound assays were conducted to assess the growth inhibition of UM-SCC-1 cells by BVZ: PCF: CuNPs.

COVARIATES

No covariates were tested in this study.

ANALYSES

The experimental data were analyzed using GraphPad Prism software (version 9.5.1). Cytotoxicity results are expressed as mean ± standard deviation, and statistical significance was determined using one-way analysis of variance (ANOVA) followed by Tukey's post hoc test. Statistical significance was set at P < .05.; State the statistical analyses used, the level of statistical significance, and the statistical software package used.

RESULTS

The ultraviolet spectrum showed a peak at 419 nm. Fourier-transform infrared confirmed conjugation with amide bands at 1643, 1535, and 1235 cm. Scanning electron microscopy showed spherical CuNPs (40-100 nm) and fibrin fibers (1-2 μm). BVZ: PCF: CuNPs decreased cell viability by 37%, with IC of 3.2 versus 5.8 μM (P < .05). Apoptosis was higher in the BVZ group (65 vs 42%, P < .05).

CONCLUSION AND RELEVANCE

BVZ: PCF: CuNP was successfully synthesized and showed greater growth inhibition of a human malignant oral keratinocyte line in vitro. Future studies should be performed to further characterize this novel nanoparticle in vitro and in vivo.

摘要

背景

靶向性的、基于生物的治疗药物旨在减轻肿瘤负担和治疗副作用。已证明基于姜黄素纳米颗粒(CuNP)的药物递送系统缀合物在体外可靶向并抑制人恶性口腔角质形成细胞的生长。

目的

本研究的目的是将生理性凝结的纤维蛋白(PCF)和CuNP与贝伐单抗(BVZ)缀合,对新形成的纳米颗粒进行表征,并测试它们在体外对人口腔癌细胞的生长抑制作用。

研究设计、设置、样本:这项体外研究于2024年6月2日至8月20日在钦奈Saveetha牙科学院和医院的细胞培养实验室White Lab进行。使用了人恶性口腔角质形成细胞系UM-SCC-1。

预测变量

主要预测变量是BVZ:PCF:CuNP纳米颗粒制剂中的BVZ。对照组由PCF:CuNP纳米颗粒组成。

主要结果变量

结果变量是BVZ:PCF:CuNP的成功合成以及UM-SCC-1细胞的生长抑制。使用紫外、傅里叶变换红外和高分辨率扫描电子显微镜对合成的纳米颗粒进行表征。进行体外细胞毒性、凋亡和划痕试验以评估BVZ:PCF:CuNP对UM-SCC-1细胞的生长抑制作用。

协变量

本研究未测试协变量。

分析

实验数据使用GraphPad Prism软件(9.5.1版)进行分析。细胞毒性结果以平均值±标准差表示,使用单因素方差分析(ANOVA),随后进行Tukey事后检验确定统计学意义。统计学显著性设定为P <.05。说明使用的统计分析、统计学显著性水平以及使用的统计软件包。

结果

紫外光谱在419nm处显示一个峰值。傅里叶变换红外证实与1643、1535和1235cm处的酰胺带缀合。扫描电子显微镜显示球形CuNP(40 - 100nm)和纤维蛋白纤维(1 - 2μm)。BVZ:PCF:CuNP使细胞活力降低37%,IC为3.2μM,而对照组为5.8μM(P <.05)。BVZ组的凋亡率更高(65%对42%,P <.05)。

结论及相关性

成功合成了BVZ:PCF:CuNP,并且在体外对人恶性口腔角质形成细胞系显示出更大的生长抑制作用。未来应进行研究以进一步在体外和体内表征这种新型纳米颗粒。

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