Advances in Black Phosphorus Quantum Dots for Cancer Research: Synthesis, Characterization, and Applications.

In the past few years, there has been notable advancement in nanotechnology, leading to the development of new materials with potential uses in the medical field, especially in cancer diagnosis, imaging, and therapy. Black phosphorus quantum dots (BPQDs) are one of the emerging nanomaterials that have generated interest due to their unique properties and potential in biomedical applications. This review aims to give a detailed overview of how BPQDs are synthesized, characterized, and utilized. The synthesis methods of BPQDs are discussed, with a focus on obtaining size-controlled and high-quality BPQDs. Two main approaches, top-down exfoliation and bottom-up techniques, are described. Despite advancements in synthesis, there are challenges hindering the practical application of BPQDs, such as poor dispersion and short durability. To address these issues, techniques to enhance biocompatibility and reduce potential toxicity, such as surface modifications, are discussed. BPQDs have potential in bioimaging as they offer higher resolution and sensitivity compared with traditional imaging agents. Their small size and expansive surface area make them suitable for drug delivery systems, enabling the effective incorporation of therapeutic substances. By functionalizing BPQDs with targeting ligands, they can selectively bind to cancer cells or tissue, making them ideal for targeted therapies. Moreover, BPQDs can serve as biosensors to detect biomarkers in bodily fluids, further expanding their biomedical applications. However, before they can be successfully translated into clinical settings, further research is needed to optimize the synthesis methods of BPQDs and evaluate their long-term safety profiles. Nonetheless, with ongoing research and development, the medical uses of BPQDs are expected to expand.

Curcumin loaded ß-cyclodextrin-magnetic graphene oxide nanoparticles decorated with folic acid receptors as a new theranostic agent to improve prostate cancer treatment.

This article presents a novel approach to treating prostate cancer using a nanocarrier composed of folic acid (FA), ß-cyclodextrin (ß-CD), and magnetic graphene oxide (MGO) as a theranostic agent. The carrier is designed to improve the solubility and bioavailability of curcumin, a potential therapeutic substance against prostate cancer. Folic acid receptors overexpressed on the surface of solid tumors, including prostate cancer, may facilitate targeted drug delivery to tumor cells while avoiding nonspecific effects on healthy tissues. The anticancer efficacy of Folic acid-curcumin@ß-CD-MGO in vitro was also examined on LNCaP (an androgen-dependent) and PC3 (an androgen-independent) prostate cancer cells. The relaxivity of nanoparticles in MRI images was also investigated as a diagnostic factor. The results showed a concentration-dependent inhibitory effect on cell proliferation, induction of oxidative damage, and apoptotic effects. Also, nanoparticle relaxometry shows that this agent can be used as a negative contrast agent in MRI images. Overall, this study represents a promising theranostic agent to improve the delivery and trace of curcumin and enhance its therapeutic potential in the treatment of prostate cancer.

Type-1 diabetes: Lessons from a decade of preclinical studies on phytotherapy.

BACKGROUND: In recent decades, numerous herbal products have been shown to have antihyperglycemic and beta cell-regenerative effects in animal studies. However, there is no clinical evidence that those products completely cure patients with type-1 diabetes (T1D). Therefore, it seems that most of the phytochemicals do not have a significant impact on human beta cells, and the results of experimental studies conducted on them may not be generalizable to the clinic. PURPOSE: The present work aims to review extensively the methods and results of preclinical studies on phytotherapy of T1D published in the last 10 years. METHODS: This paper critically analyzes the designs of studies, treatment protocols, methods of diabetes induction, characteristics of the studied animals, clinical relevance, reproducibility of research, and other aspects related to conducting preclinical studies on T1D. We discussed limitations that make many of the results of these studies not generalizable to the clinic. Finally, some recommendations were given to improve studies on the phytotherapy of T1D to avoid misleading interpretations about the antidiabetic effect of herbal compounds. CONCLUSION: This paper can be considered a practical guide for researchers interested in the field of phytotherapy of T1D to increase the reliability, reproducibility, and validity of their preclinical studies.

Moraea sisyrinchium inhibits proliferation, cell cycle, and migration of cancerous cells, and decreases angiogenesis in chick chorioallantoic membrane.

Objectives: Experimental studies reported that some plants in the genus of Moraea (Iridaceae family) show anticancer potential. This study aimed to evaluate the effects of Moraea sisyrinchium on U87 glioblastoma multiforme and HepG2 liver cancer cells. Materials and Methods: The cells were incubated for 24 hr with hydroalcoholic extract of the stem, flower, and bulb of M. sisyrinchium. Then, the cell proliferation (MTT) assay, cell cycle analysis (propidium iodide staining), cell migration test (scratch), Western blotting (Bax and Bcl-2 expression), and gelatin zymography (for matrix metalloproteinases, MMPs) were performed. Oxidative stress was evaluated by determining the levels of reactive oxygen species and lipid peroxidation. Angiogenesis was evaluated on chick embryo chorioallantoic membrane. Results: The extracts of the flower, stem, and bulb significantly decreased the proliferation of HepG2 and U87 cells. This effect was more for U87 than HepG2 and for the bulb and stem than the flower. In U87 cells, the bulb extract increased oxidative stress, cell cycle arrest, and the Bax/Bcl-2 ratio. Also, this extract suppressed the migration ability of HepG2 and U87 cells, which was associated with the inhibition of MMP2 activity. In addition, it significantly reduced the number and diameter of vessels in the chorioallantoic membrane. Liquid chromatography-mass spectrometry revealed the presence of xanthones (bellidifolin and mangiferin), flavonoids (quercetin and luteolin), isoflavones (iridin and tectorigenin), and phytosterols (e.g., stigmasterol) in the bulb. Conclusion: M. sisyrinchium bulb decreased the proliferation and survival of cancer cells by inducing oxidative stress. It also reduced the migration ability of the cells and inhibited angiogenesis.

Pro-apoptotic effect of chloroform fraction of Moraea sisyrinchium bulb against glioblastoma cells.

INTRODUCTION: Glioblastoma is a common malignant brain tumor, with limited therapeutic options. In our previous study, the Moraea sisyrinchium plant showed cytotoxicity against glioblastoma and hepatocellular carcinoma cells. Among different parts of this plant (flower, stem, and bulb), the bulb showed better anticancer potential. The present work aimed to test the anticancer activity of different fractions of the bulb extract, to determine its phytochemicals, and to study its mechanism action on glioblastoma. METHODS: The bulb extract was partitioned into different fractions using immiscible solvents. The U87 glioblastoma cells were incubated with the obtained fractions. Then, the cell proliferation assay (MTT), cell migration test (scratch), cell cycle analysis (propidium iodide staining), apoptosis/necrosis assay (annexin V/propidium iodide staining), and real-time PCR (PTEN, Akt, mTOR, BAX and BCL-2 genes) were performed. Phytochemicals were determined using liquid chromatography-mass spectroscopy. RESULTS: The chloroform fraction showed more antiproliferative effect than n-hexane, ethyl acetate, and n-butanol fractions. Also, chloroform fraction induced cell cycle arrest, increased apoptosis, and inhibited cell migration ability (P < 0.05). The expression of PTEN, mTOR, and BAX genes was significantly up-regulated, while the expression of Akt and Bcl-2 showed down-regulation. The phytochemicals identified in the chloroform fraction were mainly xanthones, phytosterols, and isoflavones. CONCLUSION: The chloroform fraction of Moraea sisyrinchium bulb inhibits the proliferation and migration of glioblastoma cells by inducing cell cycle arrest and apoptosis by upregulation of the PTEN gene and Bax/Bcl-2 ratio. The identified compounds in the chloroform fraction are potential candidates for further investigation as anticancer agents against glioblastoma.

The effects of titanium dioxide (TiO2) nanoparticles on physiological, biochemical, and antioxidant properties of Vitex plant (Vitex agnus - Castus L).

Titanium dioxide nanoparticles (TiO2NPs) are widely used in agriculture in order to increase the yield and growth characteristics of plants. This study investigated the effects of TiO2NPs on photosynthetic pigments and several biochemical activities and antioxidant enzymes of the Vitex plant. Different concentrations of nanoparticles (0, 200, 400, 600 and 800 ppm) at five levels were sprayed on Vitex plants on the 30th day of the experiment. TiO2NPs at different concentrations had positive effects on root and shoot dry weight and a negative effect on leaf dry weight. The amount of chlorophyll increased with the concentration of TiO2NPs; however, the amount of chlorophyll b showed a decreasing trend while the total chlorophyll had a constant trend. The highest amount of soluble sugar was obtained in the treatment of 200 ppm nanoparticles. The application of TiO2NPs did not have any effect on the content of proline and soluble proteins of Vitex plant. The effects of foliar TiO2NPs, compared to the control, showed a significant increase in the activity of antioxidant enzymes. In general, TiO2NPs had a favorable effect on dry matter production and some antioxidant and biochemical properties of the Vitex plant.

Recent Advances in MXene Quantum Dots: A Platform with Unique Properties for General-Purpose Functional Materials with Novel Biomedical Applications.

Developing new, high-performance materials is a prerequisite for technological advancement. In comparison to bulk materials, quantum dots have a number of good advantages due to their small size, high surface area, and quantum dimensions. Quantum dots, two-dimensional materials with lateral dimensions less than 100 nm, can be generated by the quantum confinement effect. Mxene quantum dots (MQDs) retain some of their two-dimensional characteristics. They also exhibit novel physicochemical properties, including enhanced dispersibility in aqueous and nonaqueous phases, modification or doping capabilities, and photoluminescence. MQDs, due to their unique and diverse properties, have been receiving a great deal of attention as new members of the Mxene group and wide use for biotechnology, bioimaging, optoelectronics, catalysis, cancer therapy, etc. This review aims to provide an overview of the synthesis of MQDs, their optical properties, and their cancer therapy applications. MQDs exhibit remarkable photothermal and photodynamic features and can be suitable for bioimaging. In addition to obtaining bioimaging, photothermal therapy (PTT) and photodynamic therapy (PDT) effects simultaneously, MQDs have high biocompatibility in vitro and in vivo, providing evidence of their potential clinical utility. Herein, recent developments and future prospects concerning MQDs biomedical applications are discussed.

Pathophysiology of diabetic hepatopathy and molecular mechanisms underlying the hepatoprotective effects of phytochemicals.

Patients with diabetes are at risk for liver disorders including glycogen hepatopathy, non-alcoholic fatty liver disease, cirrhosis, and hepatic fibrosis. The pathophysiological mechanisms behind diabetic hepatopathy are complex, some of them include fatty acid accumulation, increased reactive oxygen species, increased advanced glycation end-products, hyperactivity of polyol pathways, increased apoptosis and necrosis, and promotion of fibrosis. A growing number of studies have shown that herbal extracts and their active phytochemicals have antihyperglycemic properties and beneficial effects on diabetic complications. The current review, for the first time, focused on herbal agents that showed beneficial effects on diabetic hepatopathy. For example, animal studies have shown that Moringa oleifera and Morus alba improve liver function in both type-1 and type-2 diabetes. Also, evidence from clinical trials suggests that Boswellia serrata, Juglans regia, Melissa officinalis, Portulaca oleracea, Silybum marianum, Talapotaka Churna, and Urtica dioica reduce serum liver enzymes in diabetic patients. The main active ingredient of these plants to protect the liver seems to be phenolic compounds such as niazirin, chlorogenic acid, resveratrol, etc. Mechanisms responsible for the hepatoprotective activity of herbal agents include improving glucose metabolism, restoring adipokines levels, antioxidant defense, and anti-inflammatory activity. Several signaling pathways are involved in hepatoprotective effects of herbal agents in diabetes, such as phosphoinositide 3-kinase, adenosine monophosphate-activated protein kinase, mitogen-activated protein kinase, and c-Jun NH2-terminal kinase.

Nanocomposite with high adsorption activity developed using stabilized silver modified alumina and TiO2-NPs incorporated into ß-cyclodextrin-graphene oxide.

Multifunctional nanocomposites Ag/Al2O3/TiO2@ß-cyclodextrin-graphene oxide (AATG) incorporating graphene oxide sheets, TiO2, and Ag/Al2O3 nanoparticles were prepared in two steps. We benefited from the inherent properties of ß-cyclodextrin to create a stable aqueous graphene solution capable of self-assembling in situ grown TiO2 nanoparticles on graphene nanosheets. Ag/Al2O3 catalysts with a high surface-to-volume ratio were prepared by a combustion technique in solution with urea as a new fuel. The synthesized nanoparticles were also characterized by X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) surface analysis, and BJH pore analysis. FE-SEM was used to evaluate the morphology of ß-cyclodextrin-graphene oxide, Ag/Al2O3 and AATG nanoplatforms. This research examined the use of AATG as a novel nanocomposite for removing methylene blue from water and compared its effectiveness with that of TiO2@ß-cyclodextrin-graphene oxide (TG) as an intermediate material to assess the impact of the final composite and its components on absorption. The effect of pH, temperature, time, and dye concentration on the reaction rate was investigated. The results showed that at pH above 4, the adsorption rate of MB by AATG gradually increased to about 98%. The results also show that methylene blue is more effectively removed at higher temperatures, implying that the adsorption is temperature dependent and the elimination process is endothermic. The adsorption kinetics, isothermal studies, and thermodynamic analysis were also evaluated. The adsorption data showed excellent agreement with pseudo-second order models (R2 > 0.99) and the Langmuir isotherm. The AATG nanocomposites showed excellent adsorption activity, making them potential candidates for water treatment.

Curcumin-entrapped MUC-1 aptamer targeted dendrimer-gold hybrid nanostructure as a theranostic system for colon adenocarcinoma.

Gold NPs have great potential in biomedical applications. PAMAM dendrimers are spherical, hyper branched macromolecules which can encapsulate therapeutic molecules while stabilizing metal nanoparticle such as gold NPs. The aim of the current study was to investigate the theranostic capability of curcumin-loaded dendrimer-gold hybrid structure. Dendrimer-gold hybrid structure was synthesized by complexing AuCl4- ions with PEGylated amine-terminated generation 5 poly (amidoamine) dendrimer. The resultant hybrid system was loaded with curcumin. The curcumin-loaded PEGylated Au dendrimer was further conjugated to MUC-1 aptamer in order to target the colorectal adenocarcinoma in vitro and in vivo. Obtained results demonstrated that the targeted theranostic agent was accumulated in HT29 and C26 cells in vitro and showed higher cellular cytotoxicity in comparison with non-targeted system. On the other hand, in vivo experiment demonstrated the potential of targeted theranostic system in CT-scan tumor imaging as well as cancer therapy. Findings from this study suggested that MUC-1 targeted curcumin-loaded PEGylated Au dendrimers have good X-ray attenuation and is desirable probe for CT imaging while demonstrating high therapeutic index against colorectal cancer adenocarcinoma.

New cyclodextrin-based nanocarriers for drug delivery and phototherapy using an irinotecan metabolite.

SN38 is an active metabolite of irinotecan, which was approved for clinical use in metastatic colorectal cancers. However, poor aqueous solubility and inactivation at pH below 6 are the main limitations of its use. In the current study, we separately conjugated α-, ß- and γ-cyclodextrins to graphene oxide sheets to produce stable, biocompatible nanocarriers for SN38 delivery. The conjugates were coordinated with Fe3O4 in the form of superparamagnetic iron oxide nanoparticles. Then, SN38 was non-covalently conjugated to the developed nano-conjugate in order to overcome its solubility and stability problems and reduce its side effects. The loading efficiency of different formulations was between 13-22%. α-CD-GO-Fe3O4-SN38 and γ-CD-GO-Fe3O4-SN38 significantly enhanced the cytotoxicity of the conjugates compared to the free drug. Besides, combined photothermal/chemotherapy study revealed that all the designed nano-platforms reduced the HT-29 cell line viability synergistically in vitro. However, ß-CD-GO-Fe3O4-SN38 showed the highest synergistic effect compared to other formulations. In conclusion, the results of the study revealed that such combined treatment platforms might find their way as potential therapeutics to fight against cancer.