Rationale for Tailoring an Alternative Oncology Trial Using a Novel Gallium-Based Nanocomplex: Mechanistic Insights and Preclinical Challenges.

Introduction: In the fight against cancer, cisplatin is most widely used as a clinical mainstay for the chemotherapy of various human cancers. Meanwhile, its cytotoxic profile, as well as drug resistance, limits its widespread application. The goal of precision medicine is to tailor an optimized therapeutic program based on the biology of the disease. Recently, nanotechnology has been demonstrated to be promising in this scenario. Objective: The current work provides a rationale for the design of an alternative oncology trial for the treatment of hepatocarcinogenesis using a novel eco-friendly nanocomplex, namely gallic acid-coated gallium nanoparticles. Moreover, the study tests whether the antineoplastic efficacy of gallic acid-coated gallium nanoparticles could be enhanced or not when it is administrated together with cisplatin. Methods: The work comprised a series of both in vitro and in vivo investigations. The in vivo therapeutic efficacy of such treatments, against diethylnitrosamine-induced hepatocarcinogenesis, was strictly evaluated by tracking target genes expressions, iron homeostasis, diverse biomarkers alterations, and lastly, routine paraclinical investigations were also assessed. Results: The in vitro biological evaluation of gallic acid-coated gallium nanoparticles in a HepG-2 cancer cell line established its superior cytotoxicity. Else more, the results of the in vivo experiment highlighted that gallic acid-coated gallium nanoparticles could diminish key hallmarks of cancer by ameliorating most of the investigated parameters. This was well-appreciated with the histopathological findings of the liver architectures of the treated groups. Conclusions: Our findings suggest that novel biogenic Ga-based nanocomplexes may potentially present new hope for the development of alternative liver cancer therapeutics, which should attract further scientific interest.

Crystal structure and chemotherapeutic efficacy of the novel compound, gallium tetrachloride betaine, against breast cancer using nanotechnology.

The objective of this study was to investigate the antitumor efficacy of a novel synthesized compound, betaine gallium-tetrachloride (BTG), alone or combined with ZnO-nanoparticles (BTG + ZnO-NPs) on the incidence of 7, 12-dimethylbenz-anthrathene-induced mammary tumor in female rats. Crystal and molecular structure of the prepared BTG were identified using X-ray crystallography. In vitro study revealed BTG more cytotoxic than BTG + ZnO-NPs on human breast cancer (MCF-7) cell line. In vivo study demonstrated that the blood antioxidant status of tumor-bearing rats (DMBA group) was significantly lower than normal noticeable by a significant decrease in GSH content, GPx, SOD, and CAT activities associated with a significantly high MDA content. Both treatments have significantly elevated SOD and CAT activities with a concomitant decrease of MDA level compared to DMBA group. However, BTG + ZnO-NPs accentuated the decrease of GSH regarding DMBA group. The results showed also that both treatments significantly activate caspase-3 enzyme and apoptosis in mammary glands. Their administration to tumor-bearing rats was found to significantly reduce plasma iron and iron-binding capacity (TIBC) compared to DMBA group. Regarding liver function, both treatments significantly reduced the increase of ALT and AST activities compared to DMBA group. However, BTG + ZnO-NPs decreased albumin below normal level. Histopathological studies showed that normalization of tissue structures was higher in BTG than BTG + ZnO-NPs treatment. According to the results obtained, it is observed that the antitumor effect of BTG alone was as strong as BTG + ZnO-NPs and even more efficient in some aspects accordingly, a combination is not needed. Thus, the novel synthetic gallium derivatives may potentially present a new hope for the development of breast cancer therapeutics, which should attract further scientific and pharmaceutical interest.