A robust computational investigation on C₆₀ fullerene nanostructure as a novel sensor to detect SCNˉ

This study explored on the adsorption properties and electronic structure of SCNˉ via density functional theory analysis on the exterior surfaces of C₆₀ and CNTs using B3LYP functional and 6-31G** standard basis set. Then adsorption of SCNˉ through nitrogen atom on the C60 fullerene is electrostatic (₋48.02 kJ molˉ1) in comparison with the C₅₉Al fullerene that shows covalently attached to fullerene surface (₋389.10 kJ mol̄ˉ1). Our calculations demonstrate that the SCNˉ adsorption on the pristine and Al-doped single-walled CNTs are ₋173.13 and ₋334.43 kJ molˉ1, indicating that the SCNˉ can be chemically bonded on the surface of Al-doped CNTs. Moreover, the adsorption of SCNˉ on the C₆₀ surface is weaker in comparison with C₅₉B, C₅₉Al, and C₅₉Ga systems but its electronic sensitivity improved in comparison with those of C₅₉B, C₅₉Al, and C₅₉Ga fullerenes. The evaluation of adsorption energy, energy gap, and dipole moment demonstrates that the pure fullerene can be exploited in the design practice as an SCNˉ sensor and C₅₉Al can be used for SCNˉ removal application

Cancer Stem Cells And Tyrosine Kinase Receptors Directed Dual Targeted Nanoparticles For Pancreatic Ductal Adenocarcinoma Therapy And Imaging

Pancreatic ductal adenocarcinoma is the fourth leading cause of death in the US. Its survival rate is the lowest among other solid tumors due to several factors such as tumor microenvironments, low infiltrating cytotoxic cells, and the propensity of the tumor to metastasize and develop resistance against chemo and radiation therapy. Clinically, using a single agent in treating PDAC showed disappointing results. Therefore, combination therapies with different mechanisms of action are considered. Currently, gemcitabine is the centered of most combination therapies due to it is a cost-effective, well-tolerated, more effective than 5-fluorouracil (5-Flu) in terms of survival rate and showed modest activity in the patients refracted to 5-Flu. Using gemcitabine as a single agent or in combination with other agents such as cisplatin or Everolimus showed modest activity against PDAC. The reason for poor PDAC response to gemcitabine combination therapies might attributed to PDAC poor vasculature and cross-reaction between stroma and cancer cells with collagen deposition. The main goal of this study is to enhance the therapeutic benefit of gemcitabine via conjugating with SPDP-Peg4 grafted on the nanoparticles to (i) improve the systemic circulation time of gem and decrease the overall immunogenicity, (ii) reduce the nanoparticles aggregation and adsorption within the biological systems and (iii) decrease the toxicity of nanoparticles such as erythrocytes aggregation and hemolysis via minimizing nanoparticles – blood cells interactions. Also, gemcitabine anchored to targeted nanoparticles will overcome the hydrophobic drug\u27s poor cellular penetration. The gemcitabine dual-targeted nanoparticles combined with Everolimus showed an excellently synergistic effect on PDAC cell lines and enhanced the tumor regression compared to commercials Gemcitabine + Everolimus

Biocompatibility and Hemolytic Activity Studies of Synthesized Alginate-Based Polyurethanes

Many investigators have focused on the development of biocompatible polyurethanes by chemical reaction of functional groups contained in a spacer and introduced in the PU backbone or by a grafting method on graft polymerization of functional groups. In this study, alginate-based polyurethane (PU) composites were synthesized via step-growth polymerization by the reaction of hydroxyl-terminated polybutadiene (HTPB) and hexamethylene diisocyanate (HMDI). The polymer chains were further extended with blends of 1,4-butanediol (1,4-BDO) and alginate (ALG) with different mole ratios. The structures of the prepared PU samples were elucidated with FTIR and 1H NMR spectroscopy. The crystallinity of the prepared samples was evaluated with the help of X-ray diffraction (XRD). The XRD results reveal that the crystallinity of the PU samples increases when the concentration of alginate increases. Thermogravimetric (TGA) results show that samples containing a higher amount of alginate possess higher thermal stability. ALG-based PU composite samples show more biocompatibility and less hemolytic activity. Mechanical properties, contact angle, and water absorption (%) were also greatly affected

CD44 Targeted Nanomaterials for Treatment of Triple-Negative Breast Cancer

Identified as the second leading cause of cancer-related deaths among American women after lung cancer, breast cancer of all types has been the focus of numerous research studies. Even though triple-negative breast cancer (TNBC) represents 15–20% of the number of breast cancer cases worldwide, its existing therapeutic options are fairly limited. Due to the pivotal role of the presence/absence of specific receptors to luminal A, luminal B, HER-2+, and TNBC in the molecular classification of breast cancer, the lack of these receptors has accounted for the aforementioned limitation. Thereupon, in an attempt to participate in the ongoing research endeavors to overcome such a limitation, the conducted study adopts a combination strategy as a therapeutic paradigm for TNBC, which has proven notable results with respect to both: improving patient outcomes and survivability rates. The study hinges upon an investigation of a promising NPs platform for CD44 mediated theranostic that can be combined with JAK/STAT inhibitors for the treatment of TNBC. The ability of momelotinib (MMB), which is a JAK/STAT inhibitor, to sensitize the TNBC to apoptosis inducer (CFM-4.16) has been evaluated in MDA-MB-231 and MDA-MB-468. MMB + CFM-4.16 combination with a combination index (CI) ≤0.5, has been selected for in vitro and in vivo studies. MMB has been combined with CD44 directed polymeric nanoparticles (PNPs) loaded with CFM-4.16, namely CD44-T-PNPs, which selectively delivered the payload to CD44 overexpressing TNBC with a significant decrease in cell viability associated with a high dose reduction index (DRI). The mechanism underlying their synergism is based on the simultaneous downregulation of P-STAT3 and the up-regulation of CARP-1, which has induced ROS-dependent apoptosis leading to caspase 3/7 elevation, cell shrinkage, DNA damage, and suppressed migration. CD44-T-PNPs showed a remarkable cellular internalization, demonstrated by uptake of a Rhodamine B dye in vitro and S0456 (NIR dye) in vivo. S0456 was conjugated to PNPs to form CD44-T-PNPs/S0456 that simultaneously delivered CFM-4.16 and S0456 parenterally with selective tumor targeting, prolonged circulation, minimized off-target distribution

Folate Decorated Nanomicelles Loaded with a Potent Curcumin Analogue for Targeting Retinoblastoma

The aim of this study was to develop a novel folate receptor-targeted drug delivery system for retinoblastoma cells using a promising anticancer agent, curcumin-difluorinated (CDF), loaded in polymeric micelles. Folic acid was used as a targeting moiety to enhance the targeting and bioavailability of CDF. For this purpose, amphiphilic poly(styrene-co-maleic acid)-conjugated-folic acid (SMA-FA) was synthesized and utilized to improve the aqueous solubility of a highly hydrophobic, but very potent anticancer compound, CDF, and its targeted delivery to folate overexpressing cancers. The SMA-FA conjugate was first synthesized and characterized by 1H NMR, FTIR and DSC. Furthermore, the chromatographic condition (HPLC) for estimating CDF was determined and validated. The formulation was optimized to achieve maximum entrapment of CDF. The particle size of the micelles was measured and confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Cytotoxicity studies were conducted on (Y-79 and WERI-RB) retinoblastoma cells. Results showed that the solubility of CDF could be increased with the newly-synthesized polymer, and the entrapment efficiency was >85%. The drug-loaded nanomicelles exhibited an appropriate size of <200 nm and a narrow size distribution. The formulation did not show any adverse cytotoxicity on a human retinal pigment epithelial cell (ARPE-19), indicating its safety. However, it showed significant cell killing activity in both Y-79 and WERI-RB retinoblastoma cell lines, indicating its potency in killing cancer cells. In conclusion, the folic acid-conjugated SMA loaded with CDF showed promising potential with high safety and pronounced anticancer activity on the tested retinoblastoma cell lines. The newly-formulated targeted nanomicelles thus could be a viable option as an alternative approach to current retinoblastoma therapies

Olive Leaf Extracts for a Green Synthesis of Silver-Functionalized Multi-Walled Carbon Nanotubes

Green biosynthesis, one of the most dependable and cost-effective methods for producing carbon nanotubes, was used to synthesize nonhazardous silver-functionalized multi-walled carbon nanotubes (SFMWCNTs) successfully. It has been shown that the water-soluble organic materials present in the olive oil plant play a vital role in converting silver ions into silver nanoparticles (Ag-NPs). Olive-leaf extracts contain medicinal properties and combining these extracts with Ag-NPs is often a viable option for enhancing drug delivery; thus, this possibility was employed for in vitro treating cancer cells as a proof of concept. In this study, the green technique for preparing SFMWCNTs composites using plant extracts was followed. This process yielded various compounds, the most important of which were Hydroxytyrosol, Tyrosol, and Oleuropein. Subsequently, a thin film was fabricated from the extract, resulting in a natural polymer. The obtained nanomaterials have an absorption peak of 419 nm in their UV–Vis. spectra. SEM and EDS were also used to investigate the SFMWCNT nanocomposites’ morphology simultaneously. Moreover, the MTT assay was used to evaluate the ability of SFMWCNTs to suppress cancer cell viability on different cancer cell lines, MCF7 (human breast adenocarcinoma), HepG2 (human hepatocellular carcinoma), and SW620 (human colorectal cancer). Using varying doses of SFMWCNT resulted in the most significant cell viability inhibition, indicating the good sensitivity of SFMWCNTs for treating cancer cells. It was found that performing olive-leaf extraction at a low temperature in an ice bath leads to superior results, and the developed SFMWCNT nanocomposites could be potential treatment options for in vitro cancer cells

Nanomaterials for Antiangiogenic Therapies for Cancer: A Promising Tool for Personalized Medicine

Angiogenesis is one of the hallmarks of cancer. Several studies have shown that vascular endothelium growth factor (VEGF) plays a leading role in angiogenesis progression. Antiangiogenic medication has gained substantial recognition and is commonly administered in many forms of human cancer, leading to a rising interest in cancer therapy. However, this treatment method can lead to a deteriorating outcome of resistance, invasion, distant metastasis, and overall survival relative to its cytotoxicity. Furthermore, there are significant obstacles in tracking the efficacy of antiangiogenic treatments by incorporating positive biomarkers into clinical settings. These shortcomings underline the essential need to identify additional angiogenic inhibitors that target numerous angiogenic factors or to develop a new method for drug delivery of current inhibitors. The great benefits of nanoparticles are their potential, based on their specific properties, to be effective mechanisms that concentrate on the biological system and control various important functions. Among various therapeutic approaches, nanotechnology has emerged as a new strategy for treating different cancer types. This article attempts to demonstrate the huge potential for targeted nanoparticles and their molecular imaging applications. Notably, several nanoparticles have been developed and engineered to demonstrate antiangiogenic features. This nanomedicine could effectively treat a number of cancers using antiangiogenic therapies as an alternative approach. We also discuss the latest antiangiogenic and nanotherapeutic strategies and highlight tumor vessels and their microenvironments