Trends in targeted delivery of nanomaterials in colon cancer diagnosis and treatment.

Colon cancer is an adenocarcinoma, which subsequently develops into malignant tumors, if not treated properly. The current colon cancer therapy mainly revolves around chemotherapy, radiotherapy and surgery, but the search continues for more effective interventions. With the advancement of nanoparticles (NPs), it is now possible to diagnose and treat colon cancers with different types, shapes, and sizes of NPs. Nanoformulations such as quantum dots, iron oxide, polymeric NPs, dendrimers, polypeptides, gold NPs, silver NPs, platinum NPs, and cerium oxide have been either extensively used alone or in combination with other nanomaterials or drugs in colon cancer diagnosis, and treatments. These nanoformulations possess high biocompatibility and bioavailability, which makes them the most suitable candidates for cancer treatment. The size and shape of NPs are critical to achieving an effective drug delivery in cancer treatment and diagnosis. Most NPs currently are under different testing phases (in vitro, preclinical, and clinical), whereas some of them have been approved for therapeutic applications. We have comprehensively reviewed the recent advances in the applications of NPs-based formulations in colon cancer diagnosis and treatment.

Pr3+ Ion-Substituted Ni-Co Nano-Spinel Ferrites: Their Synthesis, Characterization, and Biocompatibility for Colorectal Cancer and Candidaemia.

Nanotherapeutics have attracted tremendous research interest in the modern pharmaceutical and biomedical industries due to their potential for drug development, targeted delivery, and therapeutic applications. Therefore, the current study underpins the synthesis of praseodymium ion (Pr3+)-substituted Ni0.5Co0.5Fe2O4 nano-spinel ferrites, (Co0.5Ni0.5PrxFe2-xO4 (0.0 ≤ x ≤ 0.10) NSFs, CoNiPr (x ≤ 0.10) NSFs) via the sonochemical route for its application as a nanotherapeutic treatment option. The synthesized nanomaterial was characterized using various analytical techniques, including scanning/transmission electron microscopy (SEM) and X-ray powder diffractometry (XRD). After substitution with Pr (x = 0.08), the particle size, polydispersity index, and zeta potential analysis indicated an increase in hydrodynamic diameter, with an average zeta potential value of -10.2 mV. The investigation of CoNiPr (x ≤ 0.10) NSFs on colorectal cancer (HCT-116) cells demonstrated a significant effect on cancer cell viability. The inhibitory concentration (IC50) of CoNiPr (x ≤ 0.10) NSFs was between 46 ± 0.91 and 288 ± 8.21 for HCT-116 cells. The effect of CoNiPr (x ≤ 0.10) NSFs on normal human embryonic kidney (HEK-293) cells showed a reduction in the HEK-293 cell viability; however, the cell viability was better than HCT-116. The NSFs treatment also showed morphological changes in cancer cell nuclei, as revealed by DAPI (4',6-diamidino-2-phenylindole), nuclear disintegration, and chromatic fragmentation, which are signs of apoptosis or programmed cell death. To examine the potential antifungal effects of CoNiPr NSFs on Candida albicans, known to cause candidemia among cancer patients, the viability of the cells was assessed post treatment with CoNiPr (x ≤ 0.10) NSFs. The increasing ratio of dopant had a moderate impact on the percentage of cell viability loss of 42, 44, and 43% with x = 0.06, 0.08, and 0.10, respectively. These results reinforce that increased dopant significantly impacts the antifungal properties of the synthesized nanomaterial. These findings support the idea that NSFs might be useful in pharmaceuticals.

Biocompatibility and colorectal anti-cancer activity study of nanosized BaTiO3 coated spinel ferrites.

In the present work, different nanoparticles spinel ferrite series (MFe2O4, Co0.5M0.5Fe2O4; M = Co, Mn, Ni, Mg, Cu, or Zn) have been obtained via sonochemical approach. Then, sol-gel method was employed to design core-shell magnetoelectric nanocomposites by coating these nanoparticles with BaTiO3 (BTO). The structure and morphology of the prepared samples were examined by X-ray powder diffraction (XRD), scanning electron microscope (SEM) coupled with energy dispersive X-ray spectroscopy (EDX), high-resolution transmission electron microscope (HR-TEM), and zeta potential. XRD analysis showed the presence of spinel ferrite and BTO phases without any trace of a secondary phase. Both phases crystallized in the cubic structure. SEM micrographs illustrated an agglomeration of spherical grains with nonuniformly diphase orientation and different degrees of agglomeration. Moreover, HR-TEM revealed interplanar d-spacing planes that are in good agreement with those of the spinel ferrite phase and BTO phase. These techniques along with EDX analyses confirmed the successful formation of the desired nanocomposites. Zeta potential was also investigated. The biological influence of (MFe2O4, CoMFe) MNPs and core-shell (MFe2O4@BTO, CoMFe@BTO) magnetoelectric nanocomposites were examined by MTT and DAPI assays. Post 48 h of treatments, the anticancer activity of MNPs and MENCs was investigated on human colorectal carcinoma cells (HCT-116) against the cytocompatibility of normal non-cancerous cells (HEK-293). It was established that MNPs possess anti-colon cancer capability while MENCs exhibited a recovery effect due to the presence of a protective biocompatible BTO layer. RBCs hemolytic effect of NPs has ranged from non- to low-hemolytic effect. This effect that could be attributed to the surface charge from zeta potential, also the CoMnFe possesses the stable and lowest zeta potential in comparison with CoFe2O4 and MnFe2O4 also to the protective effect of shell. These findings open up wide prospects for biomedical applications of MNPs as anticancer and MENCs as promising drug nanocarriers.

Emerging trends in the delivery of nanoformulated oxytocin across Blood-Brain barrier.

Neurological diseases are related to the central nervous system disorders and considered as serious cases. Several drugs are used to treat neurological diseases; however, to date the main issue is to design a therapeutic model which can cross the blood-brain-barrier (BBB) easily. The delivery of neuropeptides into the brain lays as one of the important routes for treating neurological disorders. Neuropeptides have been demonstrated as potential therapeutics for neurological disorders. Among numerous neuropeptides, the oxytocin (OT) hormone is of particular interest as it serves as a neurotransmitter in the brain as well as its role as a hormone. OT has a wide-range of activities in the brain and has a key role in cognitive, neuroendocrine, and social functions. However, OT does not cross the BBB readily coupled with its half-life in the blood being too short. The current literature reveals that the delivery of OT by nanoparticle-based drug delivery system (DDS) improves its efficacy. Nanoparticle based DDS are considered important tools for the targeted delivery of drugs to the brain as they lower toxicity of the drug and improve the drug efficacy. Nanoparticles are advantageous candidates for biomedical applications due to their distinctive characteristics such as quantum effects, large surface area and their ability to carry and transport the drug to its target site. OT can be delivered through oral and intranasal routes, but the bioavailability of OT inside the brain can further be enhanced by the delivery using nanoparticles. The application of nano-based delivery system not only improves the penetration of OT inside brain but also increases its half-life by the application of encapsulation and extended release. The aim of current review is to provide an overview of nanoparticle-based drug-delivery systems for the delivery of OT inside brain.

Anti-microbial and anti-cancer activities of Mn0.5Zn0.5DyxFe2-xO4 (x ≤ 0.1) nanoparticles.

Combining two or more nanoparticles is a promising approach. Previously we have reported synthesis of nanoparticles Dysprosium (Dy) substituted with manganese (Mn) zinc (Zn) by using ultrasonication method. The five different nanoparticles (NPs) Mn0.5Zn0.5DyxFe2-xO4 (x ≤ 0.1) have been structurally and morphologically characterized but there is no report on the biological application of these NPs. In the present study, we have examined the anti-cancer, anti-bacterial, and anti-fungal activities of Mn0.5Zn0.5DyxFe2-xO4 (x ≤ 0.1) NPs. Human colorectal carcinoma cells (HCT-116) were tested with different concentrations of NPs by using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. In addition, the impact of NPs was also examined on normal cells such as human embryonic kidney cells, HEK-293. After 48 h of treatment, Mn0.5Zn0.5DyxFe2-xO4 NPs (x = 0.02, 0.04 and 0.06) showed no inhibitory action on cancer cell's growth and proliferation, whereas Mn0.5Zn0.5DyxFe2-xO4 NPs (x = 0.08 and 0.1) showed profound inhibitory action on cancer cell's growth and proliferation. However, the treatment of Mn0.5Zn0.5DyxFe2-xO4 NPs on the normal cells (HEK-293) did not show cytotoxic or inhibitory action on HEK-293 cells. The treatment of Mn0.5Zn0.5DyxFe2-xO4 NPs (x ≤ 0.1) also inhibited both the bacteria (Escherichia coli ATCC35218 and Staphylococcus aureus) with lowest MIC and MBC values of 4 and 8 mg/mL and fungus (Candida albicans) with MIC and MFC values of 4 and 8 mg/mL on treatment with x = 0.08 and 0. 1.

Synthesis, Characterization, Anti-Cancer Analysis of Sr0.5Ba0.5DyxSmxFe8-2xO19 (0.00 ≤ x ≤ 1.0) Microsphere Nanocomposites.

There is enormous interest in combining two or more nanoparticles for various biomedical applications, especially in anti-cancer agent delivery. In this study, the microsphere nanoparticles were prepared (MSNPs) and their impact on cancer cells was examined. The MSNPs were prepared by using the hydrothermal method where strontium (Sr), barium (Ba), dysprosium (Dy), samarium (Sm), and iron oxide (Fe8-2xO19) were combined, and dysprosium (Dy) and samarium (Sm) was substituted with strontium (Sr) and barium (Ba), preparing Sr0.5Ba0.5DyxSmxFe8-2xO19 (0.00 ≤ x ≤ 1.0) MSNPs. The microspheres were characterized by X-ray powder diffraction (XRD), high-resolution transmission electron microscopy (HR-TEM), transmission electron microscopy (TEM), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDX) techniques. The diffraction pattern of nanohexaferrites (NHFs) reflected the signature peaks of the hexagonal structure. The XRD revealed a pure hexagonal structure without any undesired phase, which indicated the homogeneity of the products. The crystal size of the nanoparticles were in the range of 22 to 36 nm by Scherrer's equation. The SEM of MSNPs showed a semi-spherical shape with a high degree of aggregation. TEM and HR-TEM images of MSNPs verified the spherical shape morphology and structure that approved an M-type hexaferrite formation. The anti-cancer activity was examined on HCT-116 (human colorectal carcinoma) and HeLa (cervical cancer cells) using MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and post-48 h treatment of MSNPs caused a dose-dependent inhibition of HCT-116 and HeLa cell proliferation and growth. Conversely, no significant cytotoxic effect was observed on HEK-293 cells. The treatments of MSNPs also induced cancer cells DNA disintegration, as revealed by 4',6-diamidino-2-phenylindole (DAPI) staining. Finally, these findings suggest that synthesized MSNPs possess potential inhibitory actions on cancerous cells without harming normal cells.

Bactericidal and In Vitro Cytotoxicity of Moringa oleifera Seed Extract and Its Elemental Analysis Using Laser-Induced Breakdown Spectroscopy.

In the current study, we present the correlation between the capability of laser-induced breakdown spectroscopy (LIBS) to monitor the elemental compositions of plants and their biological effects. The selected plant, Moringa oleifera, is known to harbor various minerals and vitamins useful for human health and is a potential source for pharmaceutical interventions. From this standpoint, we assessed the antibacterial and in vitro cytotoxicity of the bioactive components present in Moringa oleifera seed (MOS) extract. Detailed elemental analyses of pellets of MOSs were performed via LIBS. Furthermore, the LIBS outcome was validated using gas chromatography-mass spectrometry (GC-MS). The LIBS signal was recorded, and the presence of the essential elements (Na, Ca, Se, K, Mg, Zn, P, S, Fe and Mn) in the MOSs were examined. The bactericidal efficacy of the alcoholic MOS extract was examined against Escherichia coli (E. coli) and Staphylococcus aureus(S. aureus) by agar well diffusion (AWD) assays and scanning electron microscopy (SEM), which depicted greater inhibition against Gram-positive bacteria. The validity and DNA nuclear morphology of human colorectal carcinoma cells (HCT-116) cells were evaluated via an MTT assay and DAPI staining. The MTT assay results manifested a profoundly inhibitory action of MOS extract on HCT116 cell growth. Additionally, MOS extracts produced inhibitory action in colon cancer cells (HCT-116), whereas no inhibitory action was seen using the same concentrations of MOS extract on HEK-293 cells (non-cancerous cells), suggesting that MOS extracts could be non-cytotoxic to normal cells. The antibacterial and anticancer potency of these MOS extracts could be due to the presence of various bioactive chemical complexes, such as ethyl ester and D-allose and hexadecenoic, oleic and palmitic acids, making them an ideal candidate for pharmaceutical research and applications.

Synthesis of Dy-Y co-substituted manganese­zinc spinel nanoferrites induced anti-bacterial and anti-cancer activities: Comparison between sonochemical and sol-gel auto-combustion methods.

This study described the beneficial properties of ultrasonic irradiation approach to synthesize the spinel-type Dy-Y co-substituted Mn-Zn nanospinel ferrites (NSFs). We have used two different approaches like citrate sol-gel combustion and ultrasonic irradiation routes to produced series of Mn0.5Zn0.5Fe2-2x(DyxYx)O4 (0.0 ≤ x ≤ 0.05) NSFs (DyY-MnZn NSFs). The structure and morphology of NSFs X-was examined by using XRD, EDX, SEM and TEM methods. We have found that spinel ferrites and hematite phase in DyY-MnZn NSFs produced by citrate sol-gel, while DyY-MnZn NSFs created by ultrasonic irradiation contain a pure phase of spinel ferrite. TEM analysis revealed the spherical nanoparticles with fairly uniform size. We have also analyzed the biological applications of DyY-MnZn NSFs prepared by both methods (ultrasonication and sol-gel) by examining their anti-cancer and anti-bacterial (Escherichia coli and Staphylococcus aureu) activities. We have found that both methods produced inhibitory actions on colon cancer cells (HCT-116) and bacterial cells, whereas, no inhibitory action was observed when examined on normal and non-cancerous cells (HEK-293).

Convenient Synthesis and Anticancer Activity of Methyl 2-[3-(3-Phenyl-quinoxalin-2-ylsulfanyl)propanamido]alkanoates and N-Alkyl 3-((3-Phenyl-quinoxalin-2-yl)sulfanyl)propanamides.

A series of methyl 2-[3-(3-phenyl-quinoxalin-2-ylsulfanyl)propanamido]alkanoates and their corresponding hydrazides and N-alkyl 3-((3-phenylquinoxalin-2-yl)sulfanyl)propanamides were prepared on the basis of the chemoselective Michael reaction of acrylic acid with the parent substrate 3-phenylquinoxaline-2(1H)-thione. The parent thione was produced by a convenient novel thiation method from the corresponding 3-phenylquinoxalin-2(1H)-one. The chemical structures of the newly synthesized compounds were confirmed by elemental analyses, 1H and 13C NMR. The antiproliferative activity of the synthesized compounds was tested against human HCT-116 and MCF-7 cell lines. Out of 25 screened derivatives, 10 active compounds exhibited IC50's in the range 1.9-7.52 µg/mL on the HCT-116, and 17 active compounds exhibited IC50's in the range 2.3-6.62 µg/mL on the MCF-7 cell lines compared to the reference drug doxorubicin (IC50 3.23 µg/mL). The structure-activity relationship of the tested compounds was studied through their binding affinity to the human thymidylate synthase allosteric site in silico using molecular docking and proved the quinoxaline ring as a suitable scaffold carrying a peptidomimetic side chain in position 3.