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The proposed work involves an exclusive study on the synthesis protocol, crystal structure analysis, and imaging contrast features of unique lanthanide phosphates (LnPO4). XRD and Raman spectra affirmed the ability of the proposed synthesis technique to achieve unique LnPO4 devoid of impurities. The crystal structure analysis confirms the P121/c1 space setting of NdPO4, EuPO4, GdPO4, and TbPO4 that all uniformly crystallizes in monoclinic unit cell. In a similar manner, the tetragonal crystal setting of DyPO4, ErPO4, HoPO4, and YbPO4 that unvaryingly possess the I41/amd space setting is confirmed. Under the same synthesis conditions, the monoclinic (Eu) and tetragonal (Ho) lanthanide phosphates displayed uniform rod‐like morphologies. Absorption and luminescence properties of unique LnPO4 were determined. In vitro biological studies demonstrated low toxicity levels of LnPO4 and clearly distinguished fluorescence of TbPO4 and EuPO4 in Y79, retinoblastoma cell lines. The paramagnetic response of GdPO4, NdPO4, DyPO4, TbPO4, and HoPO4 facilitated excellent magnetic resonance imaging (MRI) contrast features. Meanwhile, GdPO4, DyPO4, HoPO4, and YbPO4 possessing higher X‐ray absorption coefficient than clinical contrast Omnipaque™ exhibited high computed tomography (CT) efficiency. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1372–1383, 2019.

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Glioma is one of the most devastating and difficult-totreat brain tumors with a very poor prognosis. Despite the current treatment modalities, the overall survival rate is only 5% contributing to a high mortality rate. Nevertheless, of emerging treatment strategies, there is still a rising need for novel mitigation strategies to counteract glioma aggressiveness. One attempt towards this long-term goal was made in this study to reveal the combined efficacy of naringenin, a bioactive flavonoid on enhancing the anti-glioma potency of temozolomide in C6 glioma cells. The cytotoxic effect of temozolomide and naringenin, both individually and in combination was assessed by employing MTT assay. The synergistic effect of the drugs temozolomide and naringenin was determined by calculating the combination index. To confirm the presence of apoptotic changes in the cells at morphological level, acridine orange/ethidium bromide staining was performed. Further, the modulatory effects of the drugs on apoptotic genes, caspase-3 and BCL-2 were evaluated using quantitative real time-PCR. Interestingly, we found that the combinatorial drug treatment was in consensus and effectively inhibited the growth of C6 glioma cells in a dose-dependent manner. Furthermore, this combinatorial drug treatment significantly up-regulated the expression of the proapoptotic gene, caspase-3 and down-regulated the anti-apoptotic gene BCL-2 suggesting a shift of equilibrium towards apoptosis. Our findings suggest that naringenin can be employed as a potent drug to enhance the anti-glioma efficacy of temozolomide and could be therapeutically exploited for the management of glioma.

Background: Glioblastoma multiforme is one of the most heterogenous primary brain tumor with high mortality. Nevertheless, of the current therapeutic approaches, survival rate remains poor with 12 to 15 months following preliminary diagnosis, this warrants the need for effective treatment modality. Wnt/β-catenin pathway is presumably the most noteworthy pathway up-regulated in almost 80% GBM cases contributing to tumor-initiation, progression and survival. Therefore, therapeutic strategies targeting key components of Wnt/β-catenin cascade using established genotoxic agents like temozolomide and pharmacological inhibitors would be an effective approach to modulate Wnt/β-catenin pathway. Recently, drug repurposing by means of effective combination therapy has gained importance in various solid tumors including GBM, by targeting two or more proteins in a single pathway, thereby possessing the ability to overcome the hurdle implicated by chemo-resistance in GBM. Objective: In this context, by employing computational tools, an attempt has been carried out to speculate the novel combinations against Wnt/β-catenin signaling pathway. Methods: We have explored the binding interactions of three conventional drugs namely temozolomide, metformin, chloroquine along with three natural compounds viz., epigallocatechin gallate, naringenin and phloroglucinol on the major receptors of Wnt/β-catenin signaling. Results: It was noted that all the experimental compounds possessed profound interaction with the two major receptors of Wnt/β-catenin pathway. Conclusion: To the best of our knowledge, this study is the first of its kind to characterize the combined interactions of the afore-mentioned drugs on Wnt/β-catenin signaling in silico and this will putatively open up new avenues for combination therapies in GBM treatment.

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Glioma is the most devastating high-grade tumor of the central nervous system, with dismal prognosis. Existing treatment modality does not provide substantial benefit to patients and demands novel strategies. One of the first-line treatments for glioma, temozolomide, provides marginal benefit to glioma patients. Repurposing of existing non-cancer drugs to treat oncology patients is gaining momentum in recent years. In this study, we investigated the therapeutic benefits of combining three repurposed drugs, namely, metformin (anti-diabetic) and epigallocatechin gallate (green tea-derived antioxidant) together with temozolomide in a glioma-induced xenograft rat model. Our triple-drug combination therapy significantly inhibited tumor growth in vivo and increased the survival rate (50%) of rats when compared with individual or dual treatments. Molecular and cellular analyses revealed that our triple-drug cocktail treatment inhibited glioma tumor growth in rat model through ROS-mediated inactivation of PI3K/AKT/mTOR pathway, arrest of the cell cycle at G1 phase and induction of molecular mechanisms of caspases-dependent apoptosis.In addition, the docking analysis and quantum mechanics studies performed here hypothesize that the effect of triple-drug combination could have been attributed by their difference in molecular interactions, that maybe due to varying electrostatic potential. Thus, repurposing metformin and epigallocatechin gallate and concurrent administration with temozolomide would serve as a prospective therapy in glioma patients.