Engineering polymeric nanosystems against oral diseases

Nanotechnology and nanoparticles (NPs) are at the forefront of modern research, par-ticularly in the case of healthcare therapeutic applications. Polymeric NPs, specifically, hold high promise for these purposes, including towards oral diseases. Careful optimisation of the production of polymeric NPs, however, is required to generate a product which can be easily translated from a laboratory environment to the actual clinical usage. Indeed, considerations such as biocompati-bility, biodistribution, and biodegradability are paramount. Moreover, a pre-clinical assessment in adequate in vitro, ex vivo or in vivo model is also required. Last but not least, considerations for the scale-up are also important, together with an appropriate clinical testing pathway. This review aims to eviscerate the above topics, sourcing at examples from the recent literature to put in context the current most burdening oral diseases and the most promising polymeric NPs which would be suitable against them

Biological Characteristics and Medical Treatment of Breast Cancer in Young Women—A Featured Population: Results from the NORA Study

Background. The present paper described the biological characteristics and clinical behavior of young women in the cohort NORA study Patients and Methods. From 2000–2002, patients (N > 3500) were enrolled at 77 Italian hospitals. Women aged ≤50 years (N = 1013) were stratified into age groups (≤35, 36–40, 41–45, and 46–50 years). The relationship between age and patient characteristics, cancer presentation, and treatment was analyzed. Results. Younger women more frequently had tumors with ER/PgR-negative(χ2 = 7.07; P = .008), HER2 amplification (χ2 = 5.76; P = .01), and high (≥10%) Ki67 labelling index (χ2 = 9.53; P = .002). Positive nodal status, large tumors, and elevated Ki67 all associated with the choice for chemotherapy followed by endocrine therapy in hormone receptor-positive patients (P < .0001). At univariate analysis, ER-ve status, chemotherapy and age resulted as the only statistically significant variables (HR = 2.02, P = .004, and >40 versus ≤40, P < .0001, resp.). At multivariate analysis, after adjustment for significant clinical and pathological factors, age remains a significant prognostic variable (HR = 0.93, P = .0021). Conclusion. This cohort study suggests that age per sè is an important prognostic factor. The restricted role of early diagnosis and the aggressive behavior of cancer in this population make necessary the application of targeted medical strategies crucial

Synergistic effect induced by gold nanoparticles with polyphenols shell during thermal therapy: Macrophage inflammatory response and cancer cell death assessment

Background: In recent decades, gold nanoparticle (Au NP)-based cancer therapy has been heavily debated. The physico-chemical properties of AuNPs can be exploited in photothermal therapy, making them a powerful tool for selectively killing cancer cells. However, the synthetic side products and capping agents often induce a strong activation of the inflammatory pathways of macrophages, thus limiting their further applications in vivo. Methods: Here, we described a green method to obtain stable polyphenol-capped AuNPs (Au NPs@polyphenols), as polyphenols are known for their anti-inflammatory and anticancer properties. These NPs were used in human macrophages to test key inflammation-related markers, such as NF-κB, TNF-α, and interleukins-6 and 8. The results were compared with similar NPs obtained by a traditional chemical route (without the polyphenol coating), proving the potential of Au NPs@polyphenols to strongly promote the shutdown of inflammation. This was useful in developing them for use as heat-synergized tools in the thermal treatment of two types of cancer cells, namely, breast cancer (MCF-7) and neuroblastoma (SH-SY5Y) cells. The cell viability, calcium release, oxidative stress, HSP-70 expression, mitochondrial, and DNA damage, as well as cytoskeleton alteration, were evaluated. Results: Our results clearly demonstrate that the combined strategy markedly exerts anticancer effects against the tested cancer cell, while neither of the single treatments (only heat or only NPs) induced significant changes. Conclusions: Au NP@polyphenols may be powerful agents in cancer treatment

Determination of Pb(II) Ions in Water by Fluorescence Spectroscopy Based on Silver Nanoclusters

In this work, a method to determine Pb(II) ions in model water is presented; the method is based on the fluorescence emission of a silver nanoclusters (AgNCs) colloidal solution, which is sensitive to lead ions. The presence of Pb(II) ions causes a photoemission enhancement of the AgNCs solution dependent on the pollutant concentration. The functional dependence is logarithmic in the range from 2.5 to 40 mu M, and through the linearization of the calibration points, a linear function is determined and exploited for the extrapolation of the test Pb(II) concentrations with a precision estimated by relative standard deviation (RSD) ranging from 21% to 10% from the highest to the lowest Pb(II) quantity, respectively. Finally, inductively coupled plasma-optical emission spectroscopy (ICP-OES) successfully validated the described method. The accuracy of the method is also studied for intentionally polluted mineral waters, revealing the same trend of the model water: the lower the concentration, the higher the precision of the method

Tuning cell behavior with nanoparticle shape

We investigated how the shape of polymeric vesicles, made by the exact same material, impacts the replication activity and metabolic state of both cancer and non-cancer cell types. First, we isolated discrete geometrical structures (spheres and tubes) from a heterogeneous sample using density-gradient centrifugation. Then, we characterized the cellular internalization and the kinetics of uptake of both types of polymersomes in different cell types (either cancer or non-cancer cells). We also investigated the cellular metabolic response as a function of the shape of the structures internalized and discovered that tubular vesicles induce a significant decrease in the replication activity of cancer cells compared to spherical vesicles. We related this effect to the significant up-regulation of the tumor suppressor genes p21 and p53 with a concomitant activation of caspase 3/7. Finally, we demonstrated that combining the intrinsic shape-dependent effects of tubes with the delivery of doxorubicin significantly increases the cytotoxicity of the system. Our results illustrate how the geometrical conformation of nanoparticles could impact cell behavior and how this could be tuned to create novel drug delivery systems tailored to specific biomedical application

3,5-Diiodo-L-thyronine modulates the expression of genes of lipid metabolism in a rat model of fatty liver.

Recent reports demonstrated that 3,5-diiodo-l-thyronine (T(2)) was able to prevent lipid accumulation in the liver of rats fed a high-fat diet (HFD). In this study, we investigated how the rat liver responds to HFD and T(2) treatment by assessing the transcription profiles of some genes involved in the pathways of lipid metabolism: oxidation, storage and secretion. The mRNA levels of the peroxisome proliferator-activated receptors (PPARα, PPARγ and PPARδ), and of their target enzymes acyl-CoA oxidase and stearoyl-CoA desaturase were evaluated by real-time RT-PCR. Moreover, the expression of the adipose triglyceride lipase involved in lipid mobilisation, of the main PAT proteins acting in lipid droplet (LD) turnover, and of apoprotein B (apo B), the major protein component of very low-density lipoproteins (VLDLs) were analysed. Overall, our data demonstrated that T(2) administration to HFD rats counteracts most of the hepatic transcriptional changes that occurred in response to the excess exogenous fat. In particular, our results suggest that T(2) may prevent the pathways leading to lipid storage in LDs, promote the processes of lipid mobilisation from LDs and secretion as VLDL, in addition to the stimulation of pathways of lipid oxidation. In conclusion, our findings might give an insight into the mechanisms underlying the anti-steatotic ability of T(2) and help to define the potential therapeutic role of T(2) for preventing or treating liver steatosis