Approaches to overcome the challenges of cancer nanomedicine drug discovery process.

Reactive oxygen species (ROS) are primary effectors of cytotoxicity induced by many anti-cancer drugs. Rhythms in the pseudo-steady-state (PSS) levels of particular intracellular ROS in cancer cells and their relevance to drug effectiveness are unknown thus far. We report that the PSS levels of intracellular superoxide (SOX), an important ROS, exhibit an inherent rhythm in HCT116 colon cancer cells, which is entrained (reset) by the SOX inducer, menadione (MD). This reset was dependent on the expression of p53, and it doubled the sensitivity of the cells to MD. The period of oscillation was found to have a linear correlation with MD concentration, given by the equation, T, in h = 23.52 − 1.05 [MD concentration in µM]. Further, we developed a mathematical model to better understand the molecular mechanisms involved in rhythm reset. Biologically meaningful parameters were obtained through parameter estimation techniques; the model can predict experimental profiles of SOX, establish qualitative relations between interacting species in the system and serves as an important tool to understand the profiles of various species. The model was also able to successfully predict the rhythm reset in MD treated hepatoma cell line, HepG2.

Rhythms in the pseudo-steady state (PSS) levels of reactive species (RS), particularly superoxide and hydroxyl radicals, exist in cancer cells. The RS rhythm characteristics, particularly frequency and amplitude, are entrained (reset) by the anticancer compounds/drugs. In this work, we show for the first time that the phase of the RS rhythm at which the drug is added is significantly important in determining the cytotoxicity of anticancer compounds/drugs such as menadione and curcumin, in two different cancer cell lines. Curcumin, the more effective of the two drugs (IC 50 = 15 µM, SiHa; 6 µM, HCT116) induced reset of superoxide and hydroxyl rhythms from 15.4 h to 9 h, and 25 h to 11 h respectively, as well as caused increases in these radical levels. However, menadione (IC 50 = 20 µM, SiHa; 17 µM, HCT116) affected only the superoxide levels. Drug treatment at different time points/ phase of the RS rhythm resulted in a maximum of 27% increase in cytotoxicity, which is significant. Further, we report for the first time, an unexpected absence of a correlation between the intracellular PSS RS and antioxidant levels; thus, the practice of using antioxidant enzyme levels as surrogate markers of intracellular oxidative stress levels may need a re-consideration. Therefore, the RS rhythm could be a fundamental/generic target to manipulate for improved cancer therapy.Reactive oxygen species (RS) such as superoxide and hydroxyl radicals seem to be an important set of molecular mediators of the effectiveness of many anticancer therapies; they are also important determinants of the cellular redox status and conditions such as hypoxia 1-7 . RS are also known to regulate cellular rhythms, and the components of the cellular redox system such as glutathione, glutathione reductase and NAD + have been shown to be rhythmic [8][9][10][11] . Such rhythms along with their crosstalk with the timekeeping mechanisms control the metabolic, transcriptional and translational machinery in the cells 12,13 . Further, the rhythms and their alterations have been linked to immune gating responses, lipid peroxidation levels as well as to drug resistance observed in some treatments 4,14-19 . However, the rhythms in the pseudo-steady state (PSS) levels of the more fundamental molecules, the RS themselves, have not been reported in the above context, probably due to an incorrect perception of their utility, given their high reaction rates.The cellular antioxidant levels have been used as an indirect measure of the oxidative stress in the cells 20 , and oxidative stress is caused by an imbalance in the rates of production and consumption of reactive species 21 . The indirect measure seems to arise from an expectation based on the molecular interactions between enzymatic antioxidants and the relevant RS -e.g. superoxide dismutase (SOD) and superoxide. However, the dynamic aspects of the cell system do not seem to be considered in that expectation. For example, the rate constants of the RS reactions are many orders of magnitude higher than the synthesis...

A new, efficient, and secure clinical approach is increasingly being sought for the treatment of cancer. Nanoemulsions (NE) are projected to have a profound effect on delivering improved healthcare services with significant implications on forthcoming healthcare policies. In contrast to other drug carriers, the key value of NEs is that they can be engineered to target tumor cells and overcome the major challenge of multi-drug resistance. Multifunctional NEs are being investigated by researchers in various fields of study, primarily in the treatment of different forms of cancer. The congruent presence of NEs with contrast agents or certain dyes increases the accuracy of cancer status identification by enhancing the responsiveness of the agents; thus, they are finding application as nanotheranostics. A summary of different NEs and their documented applications in cancer therapeutics, with emphasis on breast cancer, is presented in this chapter.

In addition to being popular today in India, Litti Chokha, a traditional dish that comes from Bihar state, is now a dish of people globally. Litti appears to be baati with similar durability and shelter that makes food easy to store and carry on long journeys. The nutritional value of the different filled spices and herbs adds to the potential value of the food in nutraceuticals. In addition, chickpea is an excellent source of minerals (calcium, phosphorus, magnesium, zinc, and iron), fatty acids unsaturated, and β-carotene. Due to these properties and compatibility with wheat flour and chickpeas, Litti is suitable as an amplification agent. In this research, Remove these words development and standardization of the preparation of chickpea flour fortified Litti was studied. Nutritionally enhanced litti were prepared using wheat flour and chickpea flour incorporated in various ratios (20%–60%). Litti prepared from 40% incorporation (C2) had a higher acceptance compared to others. The variant C2 contained protein 8.20g, fat 3.22g, carbohydrate 26.83g, energy 523.0 kcal, and fiber 7.06g