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载有乳酸链球菌素的海藻酸钠-阿拉伯胶纳米颗粒对结肠癌细胞的凋亡和抗炎作用

Apoptotic and anti-inflammatory effect of nisin-loaded sodium alginate-gum arabic nanoparticles against colon cancer cells.

作者信息

Soans Sanya Hazel, Chonche Muzaffar Jahangir, Sharan Kunal, Srinivasan Asha, Archer Ann Catherine

机构信息

Department of Microbiology, JSS Academy of Higher Education and Research, Mysuru, India.

Department of Molecular Nutrition, CSIR-Central Food Technological Research Institute, Mysuru, India.

出版信息

Int J Biol Macromol. 2025 May;305(Pt 2):141747. doi: 10.1016/j.ijbiomac.2025.141747. Epub 2025 Mar 4.

Abstract

Colon cancer is one of the leading causes of mortality and morbidity worldwide. Nisin, a polycyclic antibacterial peptide and food preservative has shown potential to combat cancer. However, it is susceptible to proteolytic cleavage in the gut. The current study investigates the protective and cytotoxic effects of nisin loaded sodium alginate gum arabic nanoparticles (Nis/ALG-GA NPs) in Caco2 cells. The physicochemical properties, loading efficiency and release kinetics were studied. Cytotoxicity (MTT assay), apoptotic effect (Ethidium bromide and acridine orange staining) and internalisation (FITC tagging) were evaluated. Gene expression of apoptotic markers and IL-10 were analysed by qPCR. The Nis/ALG-GA NPs were spherical, small with a smooth outer surface and mean size of 193 ± 4 nm. The loading efficacy was 88 ± 2 % exhibiting slow sustained release of the peptide under different gut pH conditions. The IC50 value obtained was 500 μg for 48 h and 80 μg for 72 h of incubation. The Nis/ALG-GA NPs were internalised into Caco2 cells and induced apoptosis with an increased expression of bax gene and converse decrease of bcl-2 gene. Anti-inflammatory gene IL10 was upregulated upon treatment with NPs. Thus, the Nis/ALG-GA NPs may be promising oral drug delivery systems against colon cancers.

摘要

结肠癌是全球死亡率和发病率的主要原因之一。乳酸链球菌素是一种多环抗菌肽和食品防腐剂,已显示出对抗癌症的潜力。然而,它在肠道中易受蛋白水解酶的切割。本研究调查了负载乳酸链球菌素的海藻酸钠阿拉伯胶纳米颗粒(Nis/ALG-GA NPs)对Caco2细胞的保护和细胞毒性作用。研究了其理化性质、负载效率和释放动力学。评估了细胞毒性(MTT法)、凋亡效应(溴化乙锭和吖啶橙染色)和内化作用(FITC标记)。通过qPCR分析凋亡标志物和IL-10的基因表达。Nis/ALG-GA NPs呈球形,体积小,外表面光滑,平均尺寸为193±4nm。负载效率为88±2%,在不同肠道pH条件下该肽呈现缓慢持续释放。孵育48小时获得的IC50值为500μg,72小时为80μg。Nis/ALG-GA NPs被内化到Caco2细胞中并诱导凋亡,bax基因表达增加,bcl-2基因表达相反降低。用纳米颗粒处理后抗炎基因IL10上调。因此,Nis/ALG-GA NPs可能是有前景的抗结肠癌口服给药系统。

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