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具有高治疗潜力的铜配合物纳米制剂在鼠黑色素瘤模型中的应用。

Copper complex nanoformulations featuring highly promising therapeutic potential in murine melanoma models.

机构信息

Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.

School of Chemistry, Cardiff University, Main Building, Park Place, Cardiff CF10 3AT, UK.

出版信息

Nanomedicine (Lond). 2019 Apr;14(7):835-850. doi: 10.2217/nnm-2018-0388. Epub 2019 Mar 15.

Abstract

AIM

Preclinical evaluation of a cytotoxic copper (II) complex formulated in long circulating nanoliposomes for melanoma treatment.

MATERIALS & METHODS: Liposomal nanoformulations of the copper complex were characterized in terms of thermodynamic behavior (differential scanning calorimeter), pH-sensitivity (spectrophotometry) and antiproliferative effects against murine melanoma B16F10 cells in vitro. Preclinical studies were performed in a C57BL/6 syngeneic melanoma model.

RESULTS

Nanoformulations were thermodynamically stable, and CHEMS-containing nanoliposomes were pH-sensitive and preserved the antiproliferative properties of the copper compound. These nanoformulations significantly impaired tumor progression in vivo, devoid of toxic side effects, compared with control mice or mice treated with the free metallodrug.

CONCLUSION

Copper complex-containing nanoliposomes demonstrate high anticancer efficacy and safety, constituting a step forward to the development of more effective therapeutic strategies against melanoma.

摘要

目的

评价一种新型载铜(II)配合物长循环纳米脂质体的体内外抗肿瘤活性。

材料与方法

通过差示扫描量热法(differential scanning calorimeter)对载铜(II)配合物的长循环纳米脂质体进行热力学特征分析,通过分光光度法(spectrophotometry)研究其 pH 敏感性,采用体外实验研究其对小鼠黑色素瘤 B16F10 细胞的增殖抑制作用。建立 C57BL/6 近交系黑色素瘤模型,进行体内研究。

结果

纳米脂质体热力学稳定, CHEMS 载药纳米脂质体具有 pH 敏感性,能保持铜化合物的增殖抑制作用。与对照组或单纯给予游离金属药物的小鼠相比,这些纳米脂质体显著抑制肿瘤生长,且无毒性副作用。

结论

载铜(II)配合物的长循环纳米脂质体具有高效、低毒的抗肿瘤作用,为开发更有效的黑色素瘤治疗策略迈出了重要一步。

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