Augmenting apoptosis-mediated anticancer activity of lactoperoxidase and lactoferrin by nanocombination with copper and iron hybrid nanometals.
Augmenting apoptosis-mediated anticancer activity of lactoperoxidase and lactoferrin by nanocombination with copper and iron hybrid nanometals.
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DOI：
10.1038/s41598-022-17357-y
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发表时间：
2022-08-01
影响因子：
4.6
通讯作者：
Eltarahony, Marwa
中科院分区：
文献类型：
--
作者：
El-Fakharany, Esmail M.;Abu-Serie, Marwa M.;Habashy, Noha H.;Eltarahony, Marwa
医学领域迫切需要寻找低细胞毒性的生物相容纳米制剂，为多种肿瘤的治疗提供新的策略。牛乳过氧化物酶(LP)和乳铁蛋白(LF)因其抗肿瘤活性和公认的安全模式而在医学上引起了人们的关注。Lp和Lf都是合适的蛋白质，可以包覆或吸附到铜和铁纳米金属上，以开发稳定的纳米制剂，提高免疫力和强大的抗癌作用。新型纳米金属铜和铁纳米粒子嵌入到LP和LF中，形成了新型的LP-CNP和LF-FNPs纳米组合，其形状为球形，平均纳米尺寸约为21 nm。与纳米金属、LP、LF和单独的纳米蛋白(LP-CNPs或LF-FNPs)相比，LP-CNPs和LF-FNPs对Caco-2、HepG2和MCF7细胞的半数最大抑制浓度(IC50)值显著降低，显示出最高的生长抑制效果。这种纳米组合(Lp-CNPs和Lf-FNPs)的最高凋亡效应被Annexin染色的凋亡细胞和G0群体所证实，G0群体中两个特征良好的凋亡卫士(P53和Bcl2)的表达变化最强，增殖标记物(Ki-67)的抑制程度最大。此外，在计算机分析中预测，LP-CNPs和LF-FNPs增强AMP激活的蛋白激酶(AMPK，P53激活物)活性，抑制肿瘤转移相关的蛋白酶(组织蛋白酶B和基质金属蛋白酶(MMP)-9)。我们的结果首次表明，这些新的LP和LF纳米组合在它们的选择性和介导凋亡的抗癌活性方面优于铜和铁纳米金属，以及这些蛋白质的自由形式或它们各自的纳米形式。
There is an urgent need in the medicinal fields to discover biocompatible nanoformulations with low cytotoxicity, which provide new strategies for promising therapies for several types of tumors. Bovine lactoperoxidase (LP) and lactoferrin (LF) have recently attracted attention in medicine for their antitumor activities with recognized safety pattern. Both LP and LF are suitable proteins to be coated or adsorbed to Cu and Fe nanometals for developing stable nanoformulations that boost immunity and strong anticancer effects. New nanometals of Cu and Fe NPs embedded in LP and LF forming novel nanocombinations of LP-CNPs and LF-FNPs had a spherical shape with an average nanosize of about 21 nm. The combination of LP-CNPs and LF-FNPs significantly exhibited the highest growth inhibitory efficacy, in terms of effectively lowering the half-maximal inhibitory concentration (IC50) values, against Caco-2, HepG2 and MCF7 cells comparing to nanometals, LP, LF and individual nanoproteins (LP-CNPs or LF-FNPs). The highest apoptotic effect of this nanocombination (LP-CNPs and LF-FNPs) was confirmed by the highest percentages of annexin-stained apoptotic cells and G0 population with the strongest alteration in the expression of two well-characterized apoptosis guards (p53 and Bcl-2) and the maximum suppression in the proliferation marker (Ki-67). Also, the in silico analysis predicted that LP-CNPs and LF-FNPs enhanced AMP-activated protein kinase (AMPK, p53 activator) activity and inhibited cancer migration-related proteases (cathepsin B and matrix metalloproteinase (MMP)-9). Our results offer for the first time that these novel nanocombinations of LP and LF were superior in their selectivity and apoptosis-mediating anticancer activity to Cu and Fe nanometals as well as the free form of these proteins or their individual nanoforms.
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