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纳米颗粒增强型后生元:通过有效传递实现癌症治疗的革新。

Nanoparticle-enhanced postbiotics: Revolutionizing cancer therapy through effective delivery.

机构信息

Department of Pharmacy, National Yang Ming Chiao Tung University, Taipei, Taiwan.

Department of Microbiology and Immunology, Molecular Infectious Disease Research Center, Chang Gung University and Chang Gung Memorial Hospital, Taoyuan, Taiwan.

出版信息

Life Sci. 2024 Jan 15;337:122379. doi: 10.1016/j.lfs.2023.122379. Epub 2023 Dec 23.

Abstract

AIM

Gastric cancer contributes to cancer-related fatalities. Conventional chemotherapy faces challenges due to severe adverse effects, prompting recent research to focus on postbiotics, which are safer biomolecules derived from nonviable probiotics. Despite promising in vitro results, efficient in vivo delivery systems remain a challenge. This study aimed to design a potential nanoparticle (NP) formulation encapsulating the Lacticaseibacillus paracasei GMNL-133 (SGMNL-133) isolate to enhance its therapeutic efficacy in treating gastric cancer.

MAIN METHODS

We successfully isolated GMNL-133 (SGMNL-133) by optimizing the lysate extraction and column elution processes for L. paracasei GMNL-133, resulting in substantial enhancement of its capacity to inhibit the proliferation of gastric cancer cells. Additionally, we developed a potential NP utilizing arginine-chitosan and fucoidan encapsulating SGMNL-133.

KEY FINDINGS

This innovative approach protected the SGMNL-133 from degradation by gastric acid, facilitated its penetration through the mucus layer, and enabled interaction with gastric cancer cells. Furthermore, in vivo experiments demonstrated that the encapsulation of SGMNL-133 in NPs significantly enhanced its efficacy in the treatment of orthotopic gastric tumors while simultaneously reducing tissue inflammation levels.

SIGNIFICANCE

Recent research highlights postbiotics as a safe alternative, but in vivo delivery remains a challenge. Our study optimized the extraction of the lysate and column elution of GMNL-133, yielding SGMNL-133. We also developed NPs to protect SGMNL-133 from gastric acid, enhance mucus penetration, and improve the interaction with gastric cancer cells. This combination significantly enhanced drug delivery and anti-gastric tumor activity.

摘要

目的

胃癌导致与癌症相关的死亡。由于严重的不良反应,常规化疗面临挑战,这促使最近的研究集中在后生元上,后生元是一种源自非活性益生菌的更安全的生物分子。尽管体外结果很有前景,但高效的体内输送系统仍然是一个挑战。本研究旨在设计一种潜在的纳米颗粒(NP)制剂,将其包裹在副干酪乳杆菌 GMNL-133(SGMNL-133)分离株中,以增强其治疗胃癌的疗效。

主要方法

我们通过优化副干酪乳杆菌 GMNL-133 的裂解物提取和柱洗脱工艺成功分离出 GMNL-133(SGMNL-133),从而显著提高了其抑制胃癌细胞增殖的能力。此外,我们开发了一种利用精氨酸壳聚糖和褐藻糖胶包裹 SGMNL-133 的潜在 NP。

主要发现

这种创新方法保护了 SGMNL-133 免受胃酸的降解,促进了它穿透粘液层,并使其能够与胃癌细胞相互作用。此外,体内实验表明,将 SGMNL-133 包裹在 NPs 中可显著提高其治疗原位胃癌肿瘤的疗效,同时降低组织炎症水平。

意义

最近的研究强调后生元是一种安全的替代品,但体内输送仍然是一个挑战。我们的研究优化了 GMNL-133 的裂解物提取和柱洗脱,得到了 SGMNL-133。我们还开发了 NPs 来保护 SGMNL-133 免受胃酸的影响,增强对粘液的穿透,并改善与胃癌细胞的相互作用。这种组合显著增强了药物输送和抗胃癌肿瘤的活性。

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