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用于增强癌症治疗的多功能负载索拉非尼的MXene:基于化疗/光热疗法的体外和体内研究

Multifunctional sorafenib-loaded MXene for enhanced cancer therapy: In vitro and in vivo study based on chemotherapy/photothermal therapy approach.

作者信息

Elbeltagi Shehab, Al-Zharani Mohammed, Nasr Fahd A, Ismail A M, El-Tohamy Hagar M, Abdelbased Khaled M, Eldin Zienab E

机构信息

Department of Physics, Faculty of Science, New Valley University, El-Kharga 72511, Egypt.

Biology Department, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh,11623, Saudi Arabia.

出版信息

Int J Pharm. 2025 Apr 15;674:125492. doi: 10.1016/j.ijpharm.2025.125492. Epub 2025 Mar 19.

Abstract

Cancer, characterized by uncontrolled cell proliferation, remains one of the deadliest diseases. Multifunctional hybrid nanosystems that combine drugs with photothermal therapy (PTT) offer enhanced tumor treatment options through localized thermal increase and smart drug delivery (SDD). MXene, a 2D inorganic nanomaterial consisting of titanium carbide (TiC), has garnered significant interest for cancer applications. MXene was combined with the metal-organic framework MOF-UiO-67 to create MX-Uio-67. The anticancer drug sorafenib (SN) was then load onto MX-UiO-67 and coated with chitosan (CS) to form SN-MX-UiO-67@CS aiming to improve chemo-PTT mediated by near-infrared (NIR) laser irradiation. The release of SN from SN-MX-UiO-67@CS was studied at pH 4.6 and pH 7.4 conditions, both with and without NIR, over a period of 96 h. The cumulative release of SN from MX-UiO-67@CS reached 80.16 % at pH 7.4 and 93.77 % at pH 4.6 under NIR irradiation. MTT assay results demonstrated significant cytotoxicity against HepG2 cells, with SN-MX-UiO-67@CS (chemo-PTT) displaying an IC value of 22.4 µg/mL and achieving a necrosis was 36.1 % and apoptosis rate of 50.94 %, highlighting its potential as an effective anticancer agent. Furthermore, in vivo PTT via xenograft model and biodistribution studies were performed in healthy BALB/c mice under NIR. A bio-analytical technique was established utilizing HepG2 cells for the quantitative examination of SN in mice plasma, spleen, liver, heart, kidneys, tumor and lungs. A highly significant difference was observed in the plasma concentration-time curves and pharmacokinetic parameters of SN, SN-MX, and SN-MX-UiO-67following the intravenous administration of SN-MX-UiO-67@CS. Notably, the formulation exhibited higher key pharmacokinetic parameters, involving C and AUC

摘要

癌症以细胞不受控制地增殖为特征,仍然是最致命的疾病之一。将药物与光热疗法(PTT)相结合的多功能混合纳米系统,通过局部升温及智能药物递送(SDD)提供了增强的肿瘤治疗选择。MXene是一种由碳化钛(TiC)组成的二维无机纳米材料,在癌症应用方面引起了广泛关注。将MXene与金属有机框架MOF-UiO-67结合,制备出MX-Uio-67。然后将抗癌药物索拉非尼(SN)负载到MX-UiO-67上,并用壳聚糖(CS)包覆,形成SN-MX-UiO-67@CS,旨在改善近红外(NIR)激光照射介导的化学光热疗法。在pH 4.6和pH 7.4条件下,研究了有无近红外光照射时,SN从SN-MX-UiO-67@CS中的释放情况,持续96小时。在近红外照射下,MX-UiO-67@CS中SN在pH 7.4时的累积释放率达到80.16%,在pH 4.6时达到93.77%。MTT试验结果表明,SN-MX-UiO-67@CS(化学光热疗法)对HepG2细胞具有显著的细胞毒性,IC值为22.4 μg/mL,坏死率为36.1%,凋亡率为50.94%,突出了其作为有效抗癌剂的潜力。此外,在近红外光下,通过异种移植模型在健康BALB/c小鼠体内进行了光热疗法及生物分布研究。利用HepG2细胞建立了一种生物分析技术,用于定量检测小鼠血浆、脾脏、肝脏、心脏、肾脏、肿瘤和肺中的SN。静脉注射SN-MX-UiO-67@CS后,SN、SN-MX和SN-MX-UiO-67的血浆浓度-时间曲线和药代动力学参数存在极显著差异。值得注意的是,该制剂表现出更高的关键药代动力学参数,包括C和AUC

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