Novel Drug and Gene Delivery System and Imaging Agent Based on Marine Diatom Biosilica Nanoparticles.

Mesoporous silica nanoparticles (MSNs) have great potential for applications as a drug delivery system (DDS) due to their unique properties such as large pore size, high surface area, biocompatibility, biodegradability, and stable aqueous dispersion. The MSN-mediated DDS can carry chemotherapeutic agents, optical sensors, photothermal agents, short interfering RNA (siRNA), and gene therapeutic agents. The MSN-assisted imaging techniques are applicable in cancer diagnosis. However, their synthesis via a chemical route requires toxic chemicals and is challenging, time-consuming, and energy-intensive, making the process expensive and non-viable. Fortunately, nature has provided a viable alternative material in the form of biosilica from marine resources. In this review, the applications of biosilica nanoparticles synthesized from marine diatoms in the field of drug delivery, biosensing, imaging agents, and regenerative medicine, are highlighted. Insights into the use of biosilica in the field of DDSs are elaborated, with a focus on different strategies to improve the physico-chemical properties with regards to drug loading and release efficiency, targeted delivery, and site-specific binding capacity by surface functionalization. The limitations, as well as the future scope to develop them as potential drug delivery vehicles and imaging agents, in the overall therapeutic management, are discussed.

Synthetic nanoparticle-conjugated bisindoles and hydrazinyl arylthiazole as novel antiamoebic agents against brain-eating amoebae.

Balamuthia mandrillaris and Naegleria fowleri are free-living amoebae that can cause life-threatening infections involving the central nervous system. The high mortality rates of these infections demonstrate an urgent need for novel treatment options against the amoebae. Considering that indole and thiazole compounds possess wide range of antiparasitic properties, novel bisindole and thiazole derivatives were synthesized and evaluated against the amoebae. The antiamoebic properties of four synthetic compounds i.e., two new bisindoles (2-Bromo-4-(di (1H-indol-3-yl)methyl)phenol (denoted as A1) and 2-Bromo-4-(di (1H-indol-3-yl)methyl)-6-methoxyphenol (A2)) and two known thiazole (4-(3-Nitrophenyl)-2-(2-(pyridin-3-ylmethylene)hydrazinyl)thiazole (A3) and 4-(Biphenyl-4-yl)-2-(2-(1-(pyridin-4-yl)ethylidene)hydrazinyl)thiazole (A4)) were evaluated against B. mandrillaris and N. fowleri. The ability of silver nanoparticle (AgNPs) conjugation to enrich antiamoebic activities of the compounds was also investigated. The synthetic heterocyclic compounds demonstrated up to 53% and 69% antiamoebic activities against B. mandrillaris and N. fowleri respectively, while resulting in up to 57% and 68% amoebistatic activities, respectively. Antiamoebic activities of the compounds were enhanced by up to 71% and 51% against B. mandrillaris and N. fowleri respectively, after conjugation with AgNPs. These compounds exhibited potential antiamoebic effects against B. mandrillaris and N. fowleri and conjugation of synthetic heterocyclic compounds with AgNPs enhanced their activity against the amoebae.

Anticancer Compounds Derived from Marine Diatoms.

Cancer is the main cause of death worldwide, so the discovery of new and effective therapeutic agents must be urgently addressed. Diatoms are rich in minerals and secondary metabolites such as saturated and unsaturated fatty acids, esters, acyl lipids, sterols, proteins, and flavonoids. These bioactive compounds have been reported as potent anti-cancer, anti-oxidant and anti-bacterial agents. Diatoms are unicellular photosynthetic organisms, which are important in the biogeochemical circulation of silica, nitrogen, and carbon, attributable to their short growth-cycle and high yield. The biosilica of diatoms is potentially effective as a carrier for targeted drug delivery in cancer therapy due to its high surface area, nano-porosity, bio-compatibility, and bio-degradability. In vivo studies have shown no significant symptoms of tissue damage in animal models, suggesting the suitability of a diatoms-based system as a safe nanocarrier in nano-medicine applications. This review presents an overview of diatoms' microalgae possessing anti-cancer activities and the potential role of the diatoms and biosilica in the delivery of anticancer drugs. Diatoms-based antibodies and vitamin B12 as drug carriers are also elaborated.

Cellulose-hydroxyapatite carbon electrode composite for trace plumbum ions detection in aqueous and palm oil mill effluent: Interference, optimization and validation studies.

Environmental monitoring is important to determine the extent of eco-system pollution and degradation so that effective remedial strategies can be formulated. In this study, an environmentally friendly and cost-effective sensor made up of novel carbon electrode modified with cellulose and hydroxyapatite was developed for the detection of trace lead ions in aqueous system and palm oil mill effluent. Zinc, cadmium, and copper with lead were simultaneously detected using this method. The electrode exhibited high tolerance towards twelve common metal ions and three model surface active substances - sodium dodecyl sulfate, Triton X-100, and cetyltrimethylammonium bromide. Under optimum conditions, the sensor detected lead ions in palm oil mill effluent in the concentration range of 10-50 µg/L with 0.11 ±â€¯0.37 µg/L limit of detection and 0.37 ±â€¯0.37 µg/L limit of quantification. The validation using tap water, blood serum and palm oil mill effluent samples and compared with Atomic Absorption Spectroscopy, suggested excellent sensitivity of the sensor to detect lead ions in simple and complex matrices. The cellulose produced based on "green" techniques from agro-lignocellulosic wastes, in combination with hydroxyapatite, were proven effective as components in the carbon electrode composite. It has great potential in both clinical and environmental use.

Characterization of toxic metals in tobacco, tobacco smoke, and cigarette ash from selected imported and local brands in Pakistan.

In this study, concentrations of Cd, Ni, Pb, and Cr were determined in tobacco, tobacco smoke-condensate, and cigarette ash for selected brands used in Pakistan. Smoking apparatus was designed for metal extraction from cigarette smoke. Samples were digested through microwave digester and then analyzed by flame atomic absorption spectrophotometer (FAAS). Higher concentration of Ni was detected in imported brands than the counterparts in the local brands. Pb levels were however higher in local brands while significant concentration of Cd was observed in both brands. For Cr, the level in tobacco of local brands was higher than their emitted smoke, whereas imported brands showed higher level in smoke than in tobacco. The cigarette ash retained 65 to 75% of the metal and about 25 to 30% went into the body. While this study revealed the serious requirement to standardize the manufacturing of tobacco products, more importantly is the urgent need for stronger enforcements to put in place to alert the general population about the hazardous effects of cigarettes and the health risks associated with these toxic metals.

Antibacterial and Immunoregulatory Effects of Metformin against Helicobacter pylori Infection in Rat Model.

Introduction: Helicobacter pylori (H. pylori) induces gastritis by stimulating Th17 cells and related cytokines. The aim of our study was to investigate the synergistic effect of metformin with amoxicillin as an antibiotic in inhibiting H. pylori and modulating the immune response in a rat model. Methods: Forty-five male Sprague-Dawley rats were divided into seven groups and infected with H. pylori. Over the course of 14 days, all animals were treated with metformin and amoxicillin alone and in combination. The antibacterial activity of metformin was evaluated by growth curves and colony counts. The immunoregulatory effect on Treg/Th17 balance was assessed by flow cytometry, and the cytokine profile of IL-17A, IL-1ß, IL-6, IL-8, TGF-ß, and IL-10 was determined by ELISA. The effect of metformin on gene expression of cagA and IL-8 was investigated by RT-PCR. Pathological changes were assessed by hematoxylin and eosin (H&E) staining and immunohistochemical (IHC) staining. Results: Metformin showed weak antibacterial activity against clinically isolated H. pylori. However, the combination of metformin and amoxicillin (AMX) showed strong synergistic antibacterial activity (ΣFIC = 0.24). Compared with AMX, metformin reduced inflammation and tissue damage but resulted in increased bacterial growth. During metformin administration, both TGF-ß levels and Treg cells increased dramatically (P = 0.002). In synergy with AMX, metformin decreased the effective dose of antibiotic to eradicate H. pylori. Conclusions: The combination of metformin with potential antibiotics such as AMX had a positive effect on the relief of H. pylori-related inflammation by inducing Treg cells while successfully eliminating H. pylori.

Amoxicillin-docosahexaenoic acid encapsulated chitosan-alginate nanoparticles as a delivery system with enhanced biocidal activities against Helicobacter pylori and improved ulcer healing.

Encapsulation of amoxicillin (AMX) for drug delivery against Helicobacter pylori infection and aspirin-induced ulcers in rat's stomachs was performed using docosahexaenoic acid (DHA)-loaded chitosan/alginate (CA) nanoparticles (NPs) developed by ionotropic gelation method. The physicochemical analyses of the composite NPs were performed by scanning electron microscopy, Fourier transform infrared spectroscopy, zeta potential, X-ray diffraction, and atomic force microscopy. The encapsulation efficiency of AMX was increased to 76% by incorporating DHA, which resulted in a reduction in the particle size. The formed CA-DHA-AMX NPs effectively adhered to the bacteria and rat gastric mucosa. Their antibacterial properties were more potent than those of the single AMX and CA-DHA NPs as demonstrated by the in vivo assay. The composite NPs attained higher mucoadhesive potential during food intake than during fasting (p = 0.029). At 10 and 20 mg/kg AMX, the CA-AMX-DHA showed more potent activities against H. pylori than the CA-AMX, CA-DHA, and single AMX. The in vivo study showed that the effective dose of AMX was lower when DHA was included, indicating better drug delivery and stability of the encapsulated AMX. Both mucosal thickening and ulcer index were significantly higher in the groups receiving CA-DHA-AMX than in the groups receiving CA-AMX and single AMX. The presence of DHA declines the pro-inflammatory cytokines including IL-1ß, IL-6, and IL-17A. The synergistic effects of AMX and the CA-DHA formulation increased the biocidal activities against H. pylori infection and improved ulcer healing properties.

Preparation and Characterization of Novel Schiff Base Derived From 4-Nitro Benzaldehyde and Its Cytotoxic Activities.

Normal drugs exhibit activities against both normal and cancer cells. Furthermore, cancer cells may develop resistance to these drugs that alternative treatment must be explored. The main objective of this study was to examine the anticancer activity of Schiff base against Tongue Squamous Cell Carcinoma Fibroblasts (TSCCF) and normal human gingival fibroblasts (NHGF) and to propose its mechanism. A Novel Schiff base ligand was synthesized from the reaction of 5-C-2-4-NABA (5-chloro-2-((4-nitrobenzylidene) amino) benzoic acid). These Schiff bases possessed azomethine group (-HC=N-) and aromatic group (CH) as analyzed by Fourier transforms infrared (FTIR) spectroscopy and UV-Vis spectra. The in vitro cytotoxicity screening assay suggested promising activity against TSCCF with IC50 of 446.68 µg/mL, but insignificant activity against NHGF cells (IC50 of 977.24 µg/mL) after 72 h. The evidence of apoptotic induction was supported by DAPI staining of apoptotic nuclei with reduced cell numbers, suggesting that Schiff base could induce apoptotic bodies in cancer cells being observed. Based on the Schiff base structure, the anti-cancer mechanism may be attributed to the -HC=N- azomethine group. For the first time, our findings highlighted the anticancer activities of the new Schiff base against oral cancer cell lines.

Bacteria-derived chimeric toxins as potential anticancer agents.

Cancer is one of the major causes of death globally, requiring everlasting efforts to develop novel, specific, effective, and safe treatment strategies. Despite advances in recent years, chemotherapy, as the primary treatment for cancer, still faces limitations such as the lack of specificity, drug resistance, and treatment failure. Bacterial toxins have great potential to be used as anticancer agents and can boost the effectiveness of cancer chemotherapeutics. Bacterial toxins exert anticancer effects by affecting the cell cycle and apoptotic pathways and regulating tumorigenesis. Chimeric toxins, which are recombinant derivatives of bacterial toxins, have been developed to address the low specificity of their conventional peers. Through their targeting moieties, chimeric toxins can specifically and effectively detect and kill cancer cells. This review takes a comprehensive look at the anticancer properties of bacteria-derived toxins and discusses their potential applications as therapeutic options for integrative cancer treatment.

Cytotoxicity and 1H NMR metabolomics analyses of microalgal extracts for synergistic application with Tamoxifen on breast cancer cells with reduced toxicity against Vero cells.

This study evaluated the cytotoxic activity of Tamoxifen (TMX), an anti-estrogen drug, with microalgal crude extracts (MCEs) in single and synergistic application (TMX-MCEs) on MCF-7 and 4T1 breast cancer cells, and non-cancerous Vero cells. The MCEs of Nannochloropsis oculata, Tetraselmis suecica and Chlorella sp. from five different solvents (methanol, MET; ethanol, ETH; water, W; chloroform, CHL; and hexane, HEX) were developed. The TMX-MCEs-ETH and W at the 1:2 and 1:3 ratios, attained IC50 of 15.84-29.51 µg/mL against MCF-7; 13.8-31.62 µg/mL against 4T1; and 24.54-85.11 µg/mL against Vero cells. Higher late apoptosis was exhibited against MCF-7 by the TMX-N. oculata-ETH (41.15 %); and by the TMX-T. suecica-ETH (65.69 %) against 4T1 cells. The TMX-T. suecica-ETH also showed higher ADP/ATP ratios, but comparable Caspase activities to control. For Vero cells, overall apoptotic effects were lowered with synergistic application, and only early apoptosis was higher with TMX-T. suecica-ETH but at lower levels (29.84 %). The MCEs-W showed the presence of alanine, oleic acid, linoleic acid, lactic acid, and fumaric acid. Based on Principal Component Analysis (PCA), the spectral signals for polar solvents such as MET and ETH, were found in the same cluster, while the non-polar solvent CHL was with HEX, suggesting similar chemical profiles clustered for the same polarity. The CHL and HEX were more effective with N. oculata and T. suecica which were of the marine origin, while the ETH and MET were more effective with Chlorella sp., which was of the freshwater origin. The synergistic application of microalgal bioactive compounds with TMX can maintain the cytotoxicity against breast cancer cells whilst reducing the toxicity against non-cancerous Vero cells. These findings will benefit the biopharmaceutical, and functional and healthy food industries.

Integrated algal and oil palm biorefinery as a model system for bioenergy co-generation with bioproducts and biopharmaceuticals.

BACKGROUND: There has been a greater call for greener and eco-friendly processes and bioproducts to meet the 2030's core agenda on 17 global sustainable development goals. The challenge lies in incorporating systems thinking with a comprehensive worldview as a guiding principle to develop the economy, whilst taking cognisance of the need to safeguard the environment, and to embrace the socio-cultural diversity dimension as an equal component. Any discussion on climate change, destruction of eco-system and habitat for wildlife, poverty and starvation, and the spread of infectious diseases, must be addressed together with the emphasis on the development of cleaner energy, air and water, better management of resources and biodiversity, improved agro-practices for food production and distribution, and affordable health care, as the outcomes and key performance indicators to be evaluated. Strict regulation, monitoring and enforcement to minimize emission, pollution and wastage must also be put in place. CONCLUSION: This review article focuses on the research and development efforts to achieve sustainable bioenergy production, environmental remediation, and transformation of agro-materials into value-added bioproducts through the integrated algal and oil palm biorefinery. Recent development in microalgal research with nanotechnology as anti-cancer and antimicrobial agents and for biopharmaceutical applications are discussed. The life-cycle analysis in the context of palm oil mill processes is evaluated. The way forward from this integrated biorefinery concept is to strive for inclusive development strategies, and to address the immediate and pressing problems facing the Planet and the People, whilst still reaping the Profit.

Microalgal metabolites as anti-cancer/anti-oxidant agents reduce cytotoxicity of elevated silver nanoparticle levels against non-cancerous vero cells.

Heavy metal pollution has become a major concern globally as it contaminates eco-system, water networks and as finely suspended particles in air. In this study, the effects of elevated silver nanoparticle (AgNPs) levels as a model system of heavy metals, in the presence of microalgal crude extracts (MCEs) at different ratios, were evaluated against the non-cancerous Vero cells, and the cancerous MCF-7 and 4T1 cells. The MCEs were developed from water (W) and ethanol (ETH) as green solvents. The AgNPs-MCEs-W at the 4:1 and 5:1 ratios (v/v) after 48 and 72 h treatment, respectively, showed the IC50 values of 83.17-95.49 and 70.79-91.20 µg/ml on Vero cells, 13.18-28.18 and 12.58-25.7 µg/ml on MCF-7; and 16.21-33.88 and 14.79-26.91 µg/ml on 4T1 cells. In comparison, the AgNPs-MCEs-ETH formulation achieved the IC50 values of 56.23-89.12 and 63.09-91.2 µg/ml on Vero cells, 10.47-19.95 and 13.48-26.61 µg/ml on MCF-7; 14.12-50.11 and 15.13-58.88 µg/ml on 4T1 cells, respectively. After 48 and 72 h treatment, the AgNPs-MCE-CHL at the 4:1 and 5:1 ratios exhibited the IC50 of 51.28-75.85 and 48.97-69.18 µg/ml on Vero cells, and higher cytotoxicity at 10.47-16.98 and 6.19-14.45 µg/ml against MCF-7 cells, and 15.84-31.62 and 12.58-24.54 µg/ml on 4T1 cells, respectively. The AgNPs-MCEs-W and ETH resulted in low apoptotic events in the Vero cells after 24 h, but very high early and late apoptotic events in the cancerous cells. The Liquid Chromatography-Mass Spectrometry-Electrospray Ionization (LC-MS-ESI) metabolite profiling of the MCEs exhibited 64 metabolites in negative ion and 56 metabolites in positive ion mode, belonging to different classes. The microalgal metabolites, principally the anti-oxidative components, could have reduced the toxicity of the AgNPs against Vero cells, whilst retaining the cytotoxicity against the cancerous cells.

Synthesis and characterization of cellulose and hydroxyapatite-carbon electrode composite for trace plumbum ions detection and its validation in blood serum.

A novel synthesis and characterization of cellulose, hydroxyapatite and chemically-modified carbon electrode (Cellulose-HAp-CME) composite was reported for the analysis of trace Pb(II) ions detection and its validation in blood serum. The Field Emission Scanning Electron Microscopy (FESEM) analyses showed that the composite retained the orderly porous structure but with scattered particle size agglomeration. The Fourier Transform Infrared Spectroscopy (FTIR) spectra suggested the presence of functional groups associated with the bending and stretching of carbon bonds and intermolecular H-bonding. X-ray Diffraction (XRD) analyses further elucidated that the crystallite size could have influenced the properties of the electrode. Based on Thermo-gravimetric Analysis (TGA/DTG), the composites showed thermal stability with more than 60% residual content at 700°C. The sensor was successfully developed for trace Pb(II) ions detection in complex medium such as blood serum, in the physiologically relevant range of 10-60ppb, with resulting Limit of Detection (LOD) of 0.11±0.36ppb and Limit of Quantification (LOQ) of 0.36±0.36ppb. The newly fabricated electrode could be advantageous as a sensing platform with favourable electrochemical characteristics for robust, in situ and rapid environmental and clinical analyses of heavy metal ions.