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去甲斑蝥素纳米乳剂治疗同基因小鼠模型中B16F1诱导的黑色素瘤的疗效评估。

Evaluation of a Norcantharidin Nanoemulsion Efficacy for Treating B16F1-Induced Melanoma in a Syngeneic Murine Model.

作者信息

Martínez-Razo Gabriel, Pires Patrícia C, Avilez-Colin Angélica, Domínguez-López María Lilia, Veiga Francisco, Conde-Vázquez Eliezer, Paiva-Santos Ana Cláudia, Vega-López Armando

机构信息

Laboratorio de Toxicología Ambiental, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Unidad Profesional Zacatenco, Mexico City 07738, Mexico.

Department of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Azinhaga Sta. Comba, 3000-548 Coimbra, Portugal.

出版信息

Int J Mol Sci. 2025 Jan 30;26(3):1215. doi: 10.3390/ijms26031215.

DOI:10.3390/ijms26031215
PMID:39940982
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11818190/
Abstract

Melanoma, a lethal type of cancer originating from melanocytes, is the leading cause of death among skin cancers. While surgical excision of the lesions is the primary treatment for melanoma, not all cases are candidates for surgical procedures. New treatments and complementary options are necessary, given the increasing diagnosis rate. In the present study, a norcantharidin-containing nanoemulsion was developed and evaluated in vivo using a syngeneic graft murine model. Norcantharidin is the demethylated analog of cantharidin, known for its anticancer properties. Our model contemplates surgical excision surgery simulating the standard treatment and the role of the nanoemulsion as a potential adjuvant therapy. We observed a significant decrease in the growth rate of the melanoma lesion in the treated groups compared to the control group, both at the 20th and 30th days of treatment. Moreover, we evaluated the drug bioavailability in serum samples, and the results showed that norcantharidin was detectable in a range of 0.1 to 0.18 mg/mL in the treated groups. Furthermore, histopathological analysis was performed on the amputated tumors, where significant differences were found regarding size, mitosis rate, lymphocytic infiltration, and multispectral quantitative image analysis compared to the control group. If more clinical studies are conducted, the norcantharidin-containing nanoemulsion could be a potential alternative or adjuvant therapy. Topical nanosystems can become or complement standard therapies, which is needed as melanoma affects not only in terms of mortality but also the patient's morbidity and life quality.

摘要

黑色素瘤是一种起源于黑素细胞的致命性癌症,是皮肤癌死亡的主要原因。虽然手术切除病变是黑色素瘤的主要治疗方法,但并非所有病例都适合手术。鉴于诊断率不断上升,新的治疗方法和辅助选择是必要的。在本研究中,开发了一种含去甲斑蝥素的纳米乳剂,并使用同基因移植小鼠模型进行了体内评估。去甲斑蝥素是斑蝥素的去甲基类似物,以其抗癌特性而闻名。我们的模型考虑了模拟标准治疗的手术切除手术以及纳米乳剂作为潜在辅助治疗的作用。在治疗的第20天和第30天,我们观察到与对照组相比,治疗组黑色素瘤病变的生长速率显著降低。此外,我们评估了血清样本中的药物生物利用度,结果表明治疗组中去甲斑蝥素的检测范围为0.1至0.18mg/mL。此外,对切除的肿瘤进行了组织病理学分析,与对照组相比,在大小、有丝分裂率、淋巴细胞浸润和多光谱定量图像分析方面发现了显著差异。如果进行更多的临床研究,含去甲斑蝥素的纳米乳剂可能是一种潜在的替代或辅助治疗方法。局部纳米系统可以成为标准疗法或补充标准疗法,这是必要的,因为黑色素瘤不仅影响死亡率,还影响患者的发病率和生活质量。

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本文引用的文献

1
Tumor-Infiltrating iNKT Cells Activated through c-Kit/Sca-1 Are Induced by Pentoxifylline, Norcantharidin, and Their Mixtures for Killing Murine Melanoma Cells.通过c-Kit/Sca-1激活的肿瘤浸润性iNKT细胞由己酮可可碱、去甲斑蝥素及其混合物诱导产生,用于杀伤小鼠黑色素瘤细胞。
Pharmaceuticals (Basel). 2023 Oct 16;16(10):1472. doi: 10.3390/ph16101472.
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Hollow Mesoporous Silica Nanoparticles for Dual Chemo-starvation Therapy of Hepatocellular Carcinoma.中空介孔硅纳米粒子用于肝细胞癌的双重化疗-饥饿治疗。
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3
Norcantharidin Nanoemulsion Development, Characterization, and In Vitro Antiproliferation Effect on B16F1 Melanoma Cells.
去甲斑蝥素纳米乳剂的研制、表征及其对B16F1黑色素瘤细胞的体外抗增殖作用
Pharmaceuticals (Basel). 2023 Mar 28;16(4):501. doi: 10.3390/ph16040501.
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Norcantharidin toxicity profile: an in vivo murine study.去甲斑蝥素毒性特征:一项体内小鼠研究。
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Effect of nanoemulsion modification with chitosan and sodium alginate on the topical delivery and efficacy of the cytotoxic agent piplartine in 2D and 3D skin cancer models.壳聚糖和海藻酸钠纳米乳液修饰对细胞毒性药物荜茇宁在 2D 和 3D 皮肤癌模型中经皮传递和疗效的影响。
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