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载银钛黄/刚果红-白蛋白复合物用于膀胱癌抗癌治疗中的抗菌治疗。

Antibacterial Therapy by Ag Ions Complexed with Titan Yellow/Congo Red and Albumin during Anticancer Therapy of Urinary Bladder Cancer.

机构信息

Chair of Medical Biochemistry, Faculty of Medicine, Jagiellonian University Medical College, 31-034 Kraków, Poland.

Chair of Microbiology, Department of Molecular Medical Microbiology, Faculty of Medicine, Jagiellonian University Medical College, 31-121 Krakow, Poland.

出版信息

Int J Mol Sci. 2021 Dec 21;23(1):26. doi: 10.3390/ijms23010026.

DOI:10.3390/ijms23010026
PMID:35008445
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8744882/
Abstract

According to the World Health Organization report, the increasing antibiotic resistance of microorganisms is one of the biggest global health problems. The percentage of bacterial strains showing multidrug resistance (MDR) to commonly used antibiotics is growing rapidly. Therefore, the search for alternative solutions to antibiotic therapy has become critical to combat this phenomenon. It is especially important as frequent and recurring infections can cause cancer. One example of this phenomenon is urinary tract infections that can contribute to the development of human urinary bladder carcinoma. This tumor is one of the most common malignant neoplasms in humans. It occurs almost three times more often in men than in women, and in terms of the number of cases, it is the fifth malignant neoplasm after prostate, lung, colon, and stomach cancer. The risk of developing the disease increases with age. Despite the improvement of its treatment methods, the current outcome in the advanced stages of this tumor is not satisfactory. Hence, there is an urgent need to introduce innovative solutions that will prove effective even in the advanced stage of the disease. In our study, a nanosystem based on ionic silver (Ag) bound to a carrier-Titan yellow (TY) was analyzed. The possibility of binding the thus formed TY-Ag system to Congo red (CR) and albumin (BSA) was determined. TY-Ag binding to CR provides for better nanosystem solubility and enables its targeted intracellular transport and binding to immune complexes. The binding of TY-Ag or CR-TY-Ag to albumin also protects the system against the uncontrolled release of silver ions. It will also allow the delivery of silver in a targeted manner directly to the desired site in the case of intravenous administration of such a system. In this study, the MIC (Minimum Inhibitory Concentration) and MBC (Minimum Bactericidal Concentration) values of the TY-Ag or BSA-TY-Ag systems were determined in two reference strains ( and ). The paper presents nanosystems with a size of about 40-50 nm, with an intense antibacterial effect obtained at concentrations of 0.019 mM. We have also discovered that TY-Ag free or complexed with BSA (with a minimal Ag dose of 15-20 μM) inhibited cancer cells proliferation. TY-Ag complex diminished migration and effectively inhibited the T24 cell viability and induced apoptosis. On the basis of the obtained results, it has been shown that the presented systems may have anti-inflammatory and antitumor properties at the same time. TY-Ag or BSA-TY-Ag are new potential drugs and may become in future important therapeutic compounds in human urinary bladder carcinoma treatment and/or potent antimicrobial factors as an alternative to antibiotics.

摘要

根据世界卫生组织的报告,微生物对抗生素的耐药性不断增强是全球最大的健康问题之一。对常用抗生素表现出多重耐药性(MDR)的细菌菌株的比例正在迅速增加。因此,寻找抗生素治疗的替代方案对于对抗这种现象至关重要。这一点尤其重要,因为频繁和反复的感染会导致癌症。这种现象的一个例子是尿路感染,它可能导致人类膀胱癌的发生。这种肿瘤是人类中最常见的恶性肿瘤之一。它在男性中的发病率比女性高近三倍,就病例数而言,它是仅次于前列腺癌、肺癌、结肠癌和胃癌的第五大恶性肿瘤。疾病的发病风险随着年龄的增长而增加。尽管其治疗方法有所改善,但在该肿瘤的晚期阶段,目前的结果并不令人满意。因此,迫切需要引入创新的解决方案,即使在疾病的晚期阶段也能证明其有效性。在我们的研究中,分析了一种基于与载体钛黄(TY)结合的离子银(Ag)的纳米系统。确定了形成的 TY-Ag 系统与刚果红(CR)和白蛋白(BSA)结合的可能性。TY-Ag 与 CR 的结合提供了更好的纳米系统溶解性,并使其能够靶向细胞内运输并与免疫复合物结合。TY-Ag 或 CR-TY-Ag 与白蛋白的结合还可以防止系统不受控制地释放银离子。它还将允许在静脉内给予此类系统的情况下,以靶向方式输送银。在这项研究中,在两个参考菌株(和)中确定了 TY-Ag 或 BSA-TY-Ag 系统的 MIC(最小抑菌浓度)和 MBC(最小杀菌浓度)值。本文介绍了尺寸约为 40-50nm 的纳米系统,在 0.019mM 的浓度下获得了强烈的抗菌作用。我们还发现,TY-Ag 游离或与 BSA 结合(Ag 剂量最小为 15-20μM)抑制癌细胞增殖。TY-Ag 复合物减少迁移并有效抑制 T24 细胞活力并诱导细胞凋亡。基于获得的结果,表明所提出的系统可能同时具有抗炎和抗肿瘤特性。TY-Ag 或 BSA-TY-Ag 是新的潜在药物,将来可能成为人类膀胱癌治疗的重要治疗化合物和/或抗生素的替代物,成为有效的抗菌因子。

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