Efficiency of novel nanocombinations of bovine milk proteins (lactoperoxidase and lactoferrin) for combating different human cancer cell lines.

Efficiency of novel nanocombinations of bovine milk proteins (lactoperoxidase and lactoferrin) for combating different human cancer cell lines.
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DOI:
10.1038/s41598-017-16962-6
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发表时间:
2017-12-01
期刊:
影响因子:
4.6
通讯作者:
El-Fakharany EM
El-Fakharany EM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Abu-Serie MM;El-Fakharany EM

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牛乳过氧化物酶(LPO)和乳铁蛋白(LF)是适合负载或吸附到壳聚糖纳米颗粒(NP)上的蛋白质,用于制备具有有效抗癌活性的稳定纳米制剂。在本研究中,LPO 和 LF 的纳米组合与单一(游离或纳米配方)牛蛋白相比,其稳定性和活性有所改善。与其他纳米颗粒和游离蛋白相比,用 LF 包被或负载 LPO 的纳米颗粒对 Caco-2、HepG-2、MCF-7 和 PC-3 细胞产生最高的协同细胞毒性作用,而不会对正常细胞产生毒性。这种抗癌活性的协同改善是细胞凋亡依赖性的,这通过细胞形态的严重改变、膜联蛋白染色的细胞和亚 G1 群体的高百分比以及处理的癌细胞的橙色荧光的核染色来证实。此外,与 5-氟尿嘧啶 (5-FU) 处理的细胞相比,这些 NP 处理的癌细胞中特征明确的细胞增殖和凋亡守卫(NF-κB、Bcl-2 和 p53)的表达发生了显着变化。我们的研究结果首次表明,这些新的协同纳米制剂形式的 LPO 和 LF 在选择性介导细胞凋亡的抗癌作用方面优于这些蛋白质的游离形式和 5-FU。 LF 涂层或负载 LPO 的纳米颗粒是一种有前景的癌症治疗方法。
Bovine lactoperoxidase (LPO) and lactoferrin (LF) are suitable proteins to be loaded or adsorbed to chitosan nanoparticles (NPs) for preparing stable nanoformulations with potent anticancer activity. In the present study, nanocombinations of LPO and LF revealed improvement in their stability and activity compared to single (free or nanoformulated) bovine proteins. The coating or loading of LPO-loaded NPs with LF resulted in the highest synergistic cytotoxicity effect against Caco-2, HepG-2, MCF-7 and PC-3 cells in comparison with other NPs and free proteins without causing toxicity toward normal cells. This synergistic improvement in the anticancer activity was apoptosis-dependent that was confirmed by severe alterations in cellular morphology, high percentage of annexin-stained cells and sub-G1 populations as well as nuclear staining with orange fluorescence of treated cancer cells. Additionally, significant alterations in the expression of well characterized cellular proliferation and apoptosis guards (NF-κB, Bcl-2 and p53) in these NPs-treated cancer cells compared to 5-fluorouracil (5-FU) treated cells. Our findings provide for the first time that these new synergistic nanoformulated forms of LPO and LF were superior in their selective apoptosis-mediating anticancer effect than free form of these proteins and 5-FU. LF coating or loading of LPO-loaded NPs present as promising therapy for cancer.
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