Antibacterial therapy by Ag+ ions complexed with titan yellow/congo red and albumin during anticancer therapy of urinary bladder cancer

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 phenom-enon. 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 devel-oping 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 (Escherichia coli and Staphylococcus aureus). 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 mi-gration 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.