Self-Therapeutic Nanomaterials for Cancer Therapy: A Review

Cancer is a commonly lethal disease that causes many deaths every year around the world. Many strategies have been applied to treat cancer, such as surgery, radiation, and chemotherapy, but all of these therapeutic approaches are limited. Nanotechnology could provide a tremendous platform to boost the efficacy of therapeutic systems from the bench to clinical applications. The current trend of using nanomaterials for therapeutic applications is limited to drug delivery and external stimuli-responsive systems. However, several nanomaterials can reduce the growth of aggressive tumors through their self-therapeutic properties. In this review, we discuss the self-therapeutic nanomaterials that can kill cancer cells without the need for any external stimulation (heat, light, radiation, or a magnetic field) or the loading of any extra therapeutic compounds. These nanomaterials can produce reactive oxygen species, act as deoxygenating agents, or produce free radicals at tumor sites. Self-therapeutic peptide-based and other organic nanomaterials that are used to inhibit multidrug resistance (MDR) proteins, e.g., P-glycoprotein (P-gp), are also discussed. This review discusses the possible mechanisms of action of self-therapeutic nanomaterials for cancer inhibition, highlighting critical and future aspects

Nano-imaging of environmental dust in human lung tissue by soft and hard X-ray fluorescence microscopy

It is well recognized that a large number of pulmonary diseases are induced by the effects of inhaled particulates. Anthracosis is defined as an asymptomatic, mild form of pneumoconiosis caused by the accumulation of \u201cblack carbon\u201d in the lungs due to repeated exposure to air pollution or inhalation of smoke or coal dust particles. Since the human population is progressively exposed to an increasing number and doses of anthropogenic micro and nano particles/compounds, there is a pressing urgency to explore toxicological impact arising from these exposures and the molecular mechanisms driving the body defense or possible related diseases. The toxicity mechanisms are clearly related to chemical composition and physical and surface properties of materials. A combination of synchrotron radiation-based (SR-based) nano X-ray fluorescence (XRF) imaging and soft X-ray microscopy was used to chemically characterize environmental particulates (anthracosis) in lung tissues from urban subjects with the aim of better understanding the complex nature of related lungs' deposits. High-resolution XRF analyses performed at ESRF and Elettra synchrotrons allowed discriminating single particles in the heterogeneous aggregates found in the lung tissue. The small particles have variable composition resulting from the different combinations of Ti with O, K and Si, Al and Si, or Zn and Fe with O. Interestingly, simultaneous absorption and phase contrast images showed the particulate morphology and allowed to predict the presence of very dense nanoparticles or high concentration of heavy elements

Recent advances of electrochemical and optical enzyme-free glucose sensors operating at physiological conditions

Diabetes is a pathological condition that requires the continuous monitoring of glucose level in the blood. Its control has been tremendously improved by the application of point-of-care devices. Conventional enzyme-based sensors with electrochemical and optical transduction systems can successfully measure the glucose concentration in human blood, but they suffer from the low stability of the enzyme. Non-enzymatic wearable electrochemical and optical sensors, with low-cost, high stability, point-of-care testing and online monitoring of glucose levels in biological fluids, have recently been developed and can help to manage and control diabetes worldwide. Advances in nanoscience and nanotechnology have enabled the development of novel nanomaterials that can be implemented for the use in enzyme-free systems to detect glucose. This review summarizes recent developments of enzyme-free electrochemical and optical glucose sensors, as well as their respective wearable and commercially available devices, capable of detecting glucose at physiological pH conditions without the need to pretreat the biological fluids. Additionally, the evolution of electrochemical glucose sensor technology and a couple of widely used optical detection systems along with the glucose detection mechanism is also discussed. Finally, this review addresses limitations and challenges of current non-enzymatic electrochemical, optical, and wearable glucose sensor technologies and highlights opportunities for future research directions

Reliability of miRNA Analysis from Fixed and Paraffin-Embedded Tissues

In clinical practice, patients\u2019 tissues are fixed and paraffin-embedded in order to enable histological diagnosis. Nowadays, those tissues are also used for molecular characterization. Formalin is the most used fixative worldwide, and Bouin\u2019s solution in some worldwide institutions. Among molecular targets, micro RNAs (miRNAs), the single-stranded non-coding RNAs comprised of 18 to 24 nucleotides, have been demonstrated to be resistant to fixation and paraffin-embedding processes, with consequent possible application in clinical practice. In the present study, let-7e-5p, miR-423-3p, miR-92a-1-5p, miR-30d-5p, miR-155-5p, miR-200a-3p, and miR-429 were investigated in formalin and matched Bouin\u2019s solution-fixed tissues of high grade serous ovarian cancers by means of real-time and droplet digital PCR (ddPCR). Micro RNAs were detectable and analyzable in both formalin- and Bouin\u2019s-fixed specimens, but on average, higher Ct values and lower copies/\u3bcL were found in Bouin\u2019s-fixed samples. Data from formalin-fixed samples correlated significantly for most targets with Bouin\u2019s ones, except for let-7e-5p and miR-155-5p. This study shows that miRNAs are analyzable in both formalin- and Bouin\u2019s-fixed specimens, with the possibility, after proper data normalization, to compare miRNA-based data from formalin-fixed samples to those of Bouin\u2019s-fixed ones

Loss of heterozygosity at the 5,10-methylenetetrahydrofolate reductase locus in human ovarian carcinomas.

The high-affinity folate-binding protein (FBP) is primarily involved in the uptake of the 5-methyltetrahydrofolate, and its expression may be physiologically regulated by the intracellular folate content. The overexpression of FBP on the cell surface of ovarian carcinoma cells may be responsible for an increased folate uptake. We tested the hypothesis of the existence of a defect in the 5, 10-methylenetetrahydrofolate reductase (MTHFR) in ovarian tumours that could cause reduced intracellular regeneration of the 5-methyltetrahydrofolate and induce increased FBP expression. No sequence mutations were found in the MTHFR gene, but allelic deletions of this gene were frequently detected in ovarian tumours (59%). Chromosomal losses appeared to be confined to the 1p36.3 region to which the MTHFR gene maps. Although it cannot be stated that MTHFR is the target gene of the chromosomal loss involving the 1p36.3 region, a correlation between loss of heterozygosity at this locus and decrease in MTHFR activity was shown, suggesting a role of these allelic deletions in generating a biochemical defect in folate metabolism. Further studies are needed to assess further the relationship between MTHFR and FBP overexpression, but the demonstration of the alteration of a key metabolic enzyme of the folate cycle in a subset of human ovarian tumours is in accordance with the hypothesis of an altered folate metabolism in these neoplasias and might be exploited for therapeutic purposes

Malignant struma ovarii harboring a unique NRAS mutation: case report and review of the literature

Struma ovarii (SO), a rare tumor containing at least 50% of thyroid tissue, represents approximately 5% of all ovarian teratomas; its malignant transformation rate is reported to occur in up to 10% of cases and metastases occur in about 5-6% of them. We describe a 36-year old woman who underwent laparoscopic left annessectomy two years earlier because of an ovarian cyst. Follow-up imaging revealed a right adnexal mass, ascitis and peritoneal nodes that were diagnosed as comprising a malignant SO with peritoneal secondary localizations at histopathology performed after intervention. Restaging with F-18-FDG-PE T/CT scan, abdominal CT and ultrasonography showed abnormalities in the perihepatic region and presacral space and left hypochondrium localizations. The patient underwent thyroidectomy, hepatic nodulectomy and cytoreductive peritonectomy: histopathological examination did not show any malignant disease in the thyroid and confirmed the presence of peritoneal localizations due to malignant SO; molecular analysis detected NRAS Q61K mutation in exon 3, whereas no mutations were identified on the BRAF gene. The patient underwent radioiodine treatment: serum Tg was decreased at first follow-up after three months of I-131-therapy. We believe that our case raises some interesting considerations. First, pathologists should be aware of this entity and should check for the presence of point mutations suggesting an aggressive disease behavior, which could be beneficial for an optimal therapeutic approach. Second, although most of the knowledge in this field comes from case reports, efforts should be made to standardize the management of patients affected by malignant SO, including use of practice guidelines

Palladium(II)-η3-Allyl Complexes Bearing N-Trifluoromethyl N-Heterocyclic Carbenes: A New Generation of Anticancer Agents that Restrain the Growth of High-Grade Serous Ovarian Cancer Tumoroids

The first palladium organometallic compounds bearing N-trifluoromethyl N-heterocyclic carbenes have been synthesized. These η3-allyl complexes are potent antiproliferative agents against different cancer lines (for the most part, IC50 values fall in the range 0.02–0.5 μm). By choosing 1,3,5-triaza-7-phosphaadamantane (PTA) as co-ligand, we can improve the selectivity toward tumor cells, whereas the introduction of 2-methyl substituents generally reduces the antitumor activity slightly. A series of biochemical assays, aimed at defining the cellular targets of these palladium complexes, has shown that mitochondria are damaged before DNA, thus revealing a behavior substantially different from that of cisplatin and its derivatives. We assume that the specific mechanism of action of these organometallic compounds involves nucleophilic attack on the η3-allyl fragment. The effectiveness of a representative complex, 4 c, was verified on ovarian cancer tumoroids derived from patients. The results are promising: unlike carboplatin, our compound turned out to be very active and showed a low toxicity toward normal liver organoids

Self-Therapeutic Cobalt Hydroxide Nanosheets (Co(OH)2NS) for Ovarian Cancer Therapy

High-grade serous ovarian cancer (HGSOC) is one of the major life-threatening cancers in women, with a survival rate of less than 50%. So far, chemotherapy is the main therapeutic tool to cure this lethal disease; however, in many cases, it fails to cure HGSOC even with severe side effects. Self-therapeutic nanomaterials could be an effective alternative to chemotherapy, facilitated by their diverse physicochemical properties and the ability to generate reactive species for killing cancer cells. Herein, inorganic cobalt hydroxide nanosheets (Co(OH)2 NS) were synthesized by a simple solution process at room temperature, and morphological, spectroscopic, and crystallographic analyses revealed the formation of Co(OH)2 NS with good crystallinity and purity. The as-prepared Co(OH)2 NS showed excellent potency, comparable to the FDA-approved cisplatin drug to kill ovarian cancer cells. Flow cytometric analysis (nnexin V) revealed increased cellular apoptosis for Co(OH)2 NS than cobalt acetate (the precursor). Tracking experiments demonstrated that Co(OH)2 NS are internalized through the lysosome pathway, although relocalization in the cytoplasm has been observed. Hence, Co(OH)2 NS could be an effective self-therapeutic drug and open up an area for the optimization of self-therapeutic properties of cobalt nanomaterials for cancer treatment

Stard3: A prospective target for cancer therapy

Cancer is one of the major causes of death in developed countries and current therapies are based on surgery, chemotherapeutic agents, and radiation. To overcome side effects induced by chemo-and radiotherapy, in recent decades, targeted therapies have been proposed in second and even first lines. Targeted drugs act on the essential pathways involved in tumor induction, progression, and metastasis, basically all the hallmark of cancers. Among emerging pathways, the cholesterol metabolic pathway is a strong candidate for this purpose. Cancer cells have an accelerated metabolic rate and require a continuous supply of cholesterol for cell division and membrane renewal. Steroidogenic acute regulatory related lipid transfer (START) proteins are a family of proteins involved in the transfer of lipids and some of them are important in non-vesicular cholesterol transportation within the cell. The alteration of their expression levels is implicated in several diseases, including cancers. In this review, we report the latest discoveries on StAR-related lipid transfer protein domain 3 (STARD3), a member of the START family, which has a potential role in cancer, focusing on the structural and biochemical characteristics and mechanisms that regulate its activity. The role of the STARD3 protein as a molecular target for the development of cancer therapies is also discussed. As STARD3 is a key protein in the cholesterol movement in cancer cells, it is of interest to identify inhibitors able to block its activity