A novel and economical approach for the synthesis of short rod-shaped mesoporous silica nanoparticles from coal fly ash waste by Bacillus circulans MTCC 6811.

Coal fly ash (CFA) is an industrial byproduct produced during the production of electricity in thermal power plants from the burning of pulverized coal. It is considered hazardous due to the presence of toxic heavy metals while it is also considered valuable due to the presence of value-added minerals like silicates, alumina, and iron oxides. Silica nanoparticles' demands and application have increased drastically in the last decade due to their mesoporous nature, high surface area to volume ratio, etc. Here in the present research work, short rod-shaped, mesoporous silica nanoparticles (MSN) have been synthesized from coal fly ash by using Bacillus circulans MTCC 6811 in two steps. Firstly, CFA was kept with the bacterial culture for bioleaching for 25 days in an incubator shaker at 120 rpm. Secondly, the dissolved silica in the medium was precipitated with the 4 M sodium hydroxide to obtain a short rod-shaped MSN. The purification of the synthesized silica particle was done by treating them with 1 M HCl at 120 °C, for 90 min. The synthesized short rod-shaped MSN were characterized by UV-vis spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Particle size analyzer (PSA), Field emission scanning electron microscopy (FESEM), and transmission electron microscope. The microscopic techniques revealed the short rod-shaped mesoporous silica nanoparticles (MSN) for the final nano-silica, whose size varies from 40 to 80 nm, with an average size of 36 ± 5 nm. The XRD shows the crystalline nature of the synthesized MSN having a crystallite size of 36 nm. The FTIR showed the three characteristic bands in the range of 400-1100 cm-1, indicating the purity of the sample. The energy dispersive X-ray (EDX) showed 53.04 wt% oxygen and 43.42% Si along with 3.54% carbon in the final MSN. The particle size analyzer revealed that the average particle size is 368.7 nm in radius and the polydispersity index (PDI) is 0.667. Such a novel and economical approach could be helpful in the synthesis of silica in high yield with high purity from coal fly ash and other similar waste.

A cost-effective polyethylene glycol-based method for the isolation of functional edible nanoparticles from ginger rhizomes.

Edible nanoparticles (ENPs) are nano-sized vesicles derived from edible plants. These ENPs are loaded with plant derived microRNAs, protein, lipids and phytochemicals. Recently, ginger derived ENPs was shown to prevent inflammatory bowel diseases and colon cancer, in vivo, highlighting their therapeutic potential. Conventionally, differential centrifugation with an ultra-centrifugation step is employed to purify these ENPs which imposes limitation on the cost-effectiveness of their purification. Herein, we developed polyethylene glycol-6000 (PEG6000) based ginger ENP purification (PEG-ENPs) method, which eliminates the need for expensive ultracentrifugation. Using different PEG6000 concentrations, we could recover between 60% to 90% of ENPs compared to ultracentrifugation method. PEG-ENPs exhibit near identical size and zeta potential similar to ultra-ENPs. The biochemical composition of PEG-ENPs, such as proteins, lipids, small RNAs and bioactive content is comparable to that of ultra-ENPs. In addition, similar to ultra-ENPs, PEG-ENPs are efficiently taken up by the murine macrophages and protects cells from hydrogen peroxide induced oxidative stress. Since PEG has been approved as food additive, the PEG method described here will provide a cost-effective alternative to purify ENPs, which can be directly used as a dietary supplement in therapeutic formulations.

Fabrication of Ultra-Pure Anisotropic Zinc Oxide Nanoparticles via Simple and Cost-Effective Route: Implications for UTI and EAC Medications.

The purposes of this work are to evaluate the antimicrobial, antibiofilm, anticancer, and antioxidant abilities of anisotropic zinc oxide nanoparticles (ZnO NPs) synthesized by a cost-effective and eco-friendly sol-gel method. The synthesized ZnO NPs were entirely characterized by UV-Vis, XRD, FTIR, HRTEM, zeta potential, SEM mapping, BET surface analyzer, and EDX elemental analysis. Antimicrobial and antibiofilm activities of ZnO NPs were investigated against multidrug-resistant (MDR) bacteria and yeast causing serious diseases like urinary tract infection (UTI). The anticancer activity was performed against Ehrlich ascites carcinoma (EAC). Additionally, antioxidant scavenging activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) was observed. The synthesized ZnO NPs exhibited an absorption peak at 385.0 nm characteristic to the surface plasmon resonance (SPR). Data obtained from HRTEM, SEM, and XRD confirmed the anisotropic crystalline nature of the prepared ZnO NPs with an average particle size of 68.2 nm. The calculated surface area of the prepared ZnO NPs was 10.62 m2/g and the porosity was 13.16%, while pore volume was calculated to be 0.013 cm3/g and the average pore size was about 3.10 nm. The prepared ZnO NPs showed promising antimicrobial activity against all tested UTI-causing pathogens. It showed a prominent antimicrobial capability against Candida tropicalis with a zone of inhibition (ZOI) reaching 22.4 mm, 13 mm ZOI for Bacillus subtilis, and 12.5 mm ZOI for Pseudomonas aeruginosa. Additionally, the prepared ZnO NPs showed enhanced biofilm repression of about 79.33%, 72.94%, and 33.68% against B. subtilis, C. tropicalis, and P. aeruginosa, respectively. Moreover, the prepared ZnO NPs had a powerful antioxidant property with 33.0% scavenging ability after applied DPPH assay. Surprisingly, upon ZnO NPs treatment, cancer cell viability reduced from 100 to 58.5% after only 24 h due to their unique antitumor activity. Therefore, according to these outstanding properties, this study could give insights for solving serious industrial, pharmaceutical, and medical challenges, particularly in the EAC and UTI medications.

Tumor Homing Reactive Oxygen Species Nanoparticle for Enhanced Cancer Therapy.

Multifunctional nanoparticles that carry chemotherapeutic agents can be innovative anticancer therapeutic options owing to their tumor-targeting ability and high drug-loading capacity. However, the nonspecific release of toxic DNA-intercalating anticancer drugs from the nanoparticles has significant side effects on healthy cells surrounding the tumors. Herein, we report a tumor homing reactive oxygen species nanoparticle (THoR-NP) platform that is highly effective and selective for ablating malignant tumors. Sodium nitroprusside (SNP) and diethyldithiocarbamate (DDC) were selected as an exogenous reactive oxygen species (ROS) generator and a superoxide dismutase 1 inhibitor, respectively. DDC-loaded THoR-NP, in combination with SNP treatment, eliminated multiple cancer cell lines effectively by the generation of peroxynitrite in the cells (>95% cell death), as compared to control drug treatments of the same concentration of DDC or SNP alone (0% cell death). Moreover, the magnetic core (ZnFe2O4) of the THoR-NP can specifically ablate tumor cells (breast cancer cells) via magnetic hyperthermia, in conjunction with DDC, even in the absence of any exogenous RS supplements. Finally, by incorporating iRGD peptide moieties in the THoR-NP, integrin-enriched cancer cells (malignant tumors, MDA-MB-231) were effectively and selectively killed, as opposed to nonmetastatic tumors (MCF-7), as confirmed in a mouse xenograft model. Hence, our strategy of using nanoparticles embedded with ROS-scavenger-inhibitor with an exogenous ROS supplement is highly selective and effective cancer therapy.

A novel simple biosensor containing silver nanoparticles/propolis (bee glue) for microRNA let-7a determination.

A novel sensitive electrochemical sensor for microRNAlet-7a detection in normal serum samples, hepatocellular carcinoma patients and human liver cancer cells, has been excellently synthesized. The sensor constructed of carbon paste (CP) amended with silver nanoparticles (AgNPs) and extracted propolis (bee glue). The AgNPs/P modified carbon paste electrode (APCPE) displayed a high electrocatalytic activity in a Britton Robinson (BR) buffer (pH = 7.4). The techniques utilized to prepare this work are square wave voltammetry (SWV) and electrochemical impedance spectroscopy (EIS). Surface characteristics were achieved using scanning (SEM), Fourier-transform infrared spectroscopy (FTIR), Spectrophotometer, transmission (TEM) electron microscope, energy dispersive X-ray analysis (EDX) and elemental mapping (EM) techniques. Under optimal conditions, the suggested sensor exhibits good rapid and sensible response reaching a very low detection limit of 10-3 femtomolar.

Paclitaxel as Albumin-Bound Nanoparticles with Gemcitabine for Untreated Metastatic Pancreatic Cancer: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

As part of the single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited Celgene Ltd to submit clinical and cost-effectiveness evidence for paclitaxel as albumin-bound nanoparticles (Nab-Pac) in combination with gemcitabine (Nab-Pac + Gem) for patients with untreated metastatic pancreatic cancer. The STA was a review of NICE's 2015 guidance (TA360) in which Nab-Pac + Gem was not recommended for patients with untreated metastatic pancreatic cancer. The review was prompted by a proposed Patient Access Scheme (PAS) discount on the price of Nab-Pac and new evidence that might lead to a change in the guidance. The Liverpool Reviews and Implementation Group at the University of Liverpool was the Evidence Review Group (ERG). This article summarises the ERG's review of the company's evidence submission for Nab-Pac + Gem, and the Appraisal Committee (AC) decision. The final scope issued by NICE listed three comparators: gemcitabine monotherapy (Gem), gemcitabine in combination with capecitabine (Gem + Cap), and a combination of oxaliplatin, irinotecan, leucovorin and fluorouracil (FOLFIRINOX). Clinical evidence for the comparison of Nab-Pac + Gem versus Gem was from the phase III CA046 randomized controlled trial. Analysis of progression-free survival (PFS) and overall survival (OS) showed statistically significant improvement for patients treated with Nab-Pac + Gem versus Gem. Clinical evidence for the comparison of Nab-Pac + Gem versus FOLFIRINOX and versus Gem + Cap was derived from a network meta-analysis (NMA). Results of the NMA did not indicate a statistically significant difference in OS or PFS for the comparison of Nab-Pac + Gem versus either Gem + Cap or FOLFIRINOX. The ERG's main concerns with the clinical effectiveness evidence were difficulties in identifying the patient population for whom treatment with Nab-Pac + Gem is most appropriate, and violation of the proportional hazards (PH) assumption in the CA046 trial. The ERG highlighted methodological issues in the cost-effectiveness analysis pertaining to the modelling of survival outcomes, estimation of drug costs and double counting of adverse-event disutilities. The AC accepted all the ERG's amendments to the company's cost-effectiveness model; however, these did not make important differences to the incremental cost-effectiveness ratios (ICERs). The company's base-case ICER was £46,932 per quality-adjusted life-year (QALY) gained for the comparison of Nab-Pac + Gem versus Gem. Treatment with Nab-Pac + Gem was dominated both by treatment with Gem + Cap and with FOLFIRINOX in the company's base case. The AC concluded that the most plausible ICER for treatment with Nab-Pac + Gem versus Gem was in the range of £41,000-£46,000 per QALY gained. The AC concluded that Nab-Pac + Gem was not cost effective compared with Gem + Cap or FOLFIRINOX, and accepted that treatment with Nab-Pac + Gem met the end-of-life criteria versus Gem but did not consider Nab-Pac + Gem to meet the end-of-life criteria compared with Gem + Cap or FOLFIRINOX. The AC also concluded that although patients who would receive Nab-Pac + Gem rather than FOLFIRINOX or Gem + Cap were difficult to distinguish, they were identifiable in clinical practice. The AC recommended treatment with Nab-Pac + Gem for patients with untreated metastatic pancreatic cancer for whom other combination chemotherapies were unsuitable and who would otherwise receive Gem.

Targeting of metastasis-promoting tumor-associated fibroblasts and modulation of pancreatic tumor-associated stroma with a carboxymethylcellulose-docetaxel nanoparticle.

Pancreatic ductal adenocarcinomas are characterized by the desmoplastic reaction, a dense fibrous stroma that has been shown to be supportive of tumor cell growth, invasion, and metastasis, and has been associated with resistance to chemotherapy and reduced patient survival. Here, we investigated targeted depletion of stroma for pancreatic cancer therapy via taxane nanoparticles. Cellax-DTX polymer is a conjugate of docetaxel (DTX), polyethylene glycol (PEG), and acetylated carboxymethylcellulose, a construct which condenses into well-defined 120nm particles in an aqueous solution, and is suitable for intravenous injection. We examined Cellax-DTX treatment effects in highly stromal primary patient-derived pancreatic cancer xenografts and in a metastatic PAN02 mouse model of pancreatic cancer, focusing on specific cellular interactions in the stroma, pancreatic tumor growth and metastasis. Greater than 90% of Cellax-DTX particles accumulate in smooth muscle actin (SMA) positive cancer-associated fibroblasts which results in long-term depletion of this stromal cell population, an effect not observed with Nab-paclitaxel (Nab-PTX). The reduction in stromal density leads to a >10-fold increase in tumor perfusion, reduced tumor weight and a reduction in metastasis. Consentingly, Cellax-DTX treatment increased survival when compared to treatment with gemcitabine or Nab-PTX in a metastatic PAN02 mouse model. Cellax-DTX nanoparticles interact with the tumor-associated stroma, selectively interacting with and depleting SMA positive cells and macrophage, effects of which are associated with significant changes in tumor progression and metastasis.

Soft matter assemblies as nanomedicine platforms for cancer chemotherapy: a journey from market products towards novel approaches.

The current review aims to outline the likely medical applications of nanotechnology and the potential of the emerging field of nanomedicine. Nanomedicine can be defined as the investigation area encompassing the design of diagnostics and therapeutics at the nanoscale, including nanobots, nanobiosensors, nanoparticles and other nanodevices, for the remediation, prevention and diagnosis of a variety of illnesses. The ultimate goal of nanomedicine is to improve patient quality-of-life. Because nanomedicine includes the rational design of an enormous number of nanotechnology-based products focused on miscellaneous diseases, a variety of nanomaterials can be employed. Therefore, this review will focus on recent advances in the manufacture of soft matterbased nanomedicines specifically designed to improve diagnostics and cancer chemotherapy efficacy. It will be particularly highlighted liposomes, polymer-drug conjugates, drug-loaded block copolymer micelles and biodegradable polymeric nanoparticles, emphasizing the current investigations and potential novel approaches towards overcoming the remaining challenges in the field as well as formulations that are in clinical trials and marketed products.

The emerging potential of by-products as platforms for drug delivery systems.

Natural resources are widely used as raw materials by industries. In most cases, abundant byproducts with low economic interest are also generated from agro-industrial supply chains. There are several examples for the rational use of agro-industrial byproducts in the nanobiotechnology field aiming for the development of novel products and high value added processes. Such raw materials include carapaces, pelages, blood, bagasses, and straws. Molecules from such materials (e.g. chitosan, cellulose, and albumin) are used as scaffolds of unprecedented novel nanostructure. Research efforts comprising a combination of sustainability, nanobiotechnology, and nanomedicine have emerged. One major area in nano-biotechnological research of agro-industrial byproducts is represented by the field of drug delivery systems (DDS). Among the main advantages of agro-industrial byproducts used as drug carriers are their abundance; low price; high biocompatibility; good biodegradability; moderate bioresorbability, associated with reduced systemic toxicity or even no toxicity; and often bioactivity. The goal of these efforts includes not only the possibility to characterize and manipulate matter on the nanoscale, but also to develop sustainable products and processes, including the development of platforms for drug delivery aiming for the treatment of pathologies such as cancer and diabetes. Indeed, there is great hope that the use of agro-industrial byproducts in nanobiotechnology will increase not only agricultural and livestock productivity, but will also contribute to other areas such as the development of DDS with new properties and low production costs; and sustainable environmental management due to the reuse of industrial discharged byproducts. This review will compile current findings on the use of byproducts as building blocks for modern drug carrier systems, emphasizing the challenges and promising applications.

Life cycle and human health risk assessments as tools for decision making in the design and implementation of nanofiltration in drinking water treatment plants.

A combined methodology using life cycle assessment (LCA) and human health risk assessment (HHR) is proposed in order to select the percentage of water in drinking water treatment plants (DWTP) that should be nanofiltered (NF). The methodological approach presented here takes into account environmental and social benefit criteria evaluating the implementation of new processes into conventional ones. The inclusion of NF process improves drinking water quality, reduces HHR but, in turn, increases environmental impacts as a result of energy and material demand. Results from this study lead to balance the increase of the impact in various environmental categories with the reduction in human health risk as a consequence of the respective drinking water production and consumption. From an environmental point of view, the inclusion of NF and recommended pretreatments to produce 43% of the final drinking water means that the environmental impact is nearly doubled in comparison with conventional plant in impact categories severely related with electricity production, like climate change. On the other hand, the carcinogenic risk (HHR) associated to trihalomethane formation potential (THMFP) decreases with the increase in NF percentage use. Results show a reduction of one order of magnitude for the carcinogenic risk index when 100% of drinking water is produced by NF.

Clinical and economic implications of the use of nanoparticle paclitaxel (Nanoxel) in India.

Paclitaxel (Taxol), one of the most commonly used chemotherapeutic agents, is poorly soluble in water and requires cremophor, which often causes infusion reactions, as a solvent. Nanoxel, a nanoparticle formulation of the taxane, has been approved by the Indian regulatory authority. In the present article, we aim to describe the experience with the use of Nanoxel in India and its clinical and economic implications. We present three retrospective series in a common practice environment and an economic model. The first series shows no reactions in 596 Nanoxel infusions; the second series shows comparable adverse events other than infusion reactions between 83 patients who received Nanoxel and 32 treated with conventional paclitaxel. The third reveals comparable clinical outcomes for 51 patients treated with Nanoxel or conventional paclitaxel for gastroesophageal tumors. Finally, we describe an economic model which estimates savings of 21 580 Indian rupees per cycle with Nanoxel vis-à-vis conventional paclitaxel in the treatment of solid tumors in India. In conclusion, in an era in which the greatest challenge we face as medical oncologists is how to conciliate hard-won and incremental--but small--improvements in survival with exponentially rising drugs costs, it is refreshing to see a potential new formulation of a commonly used drug that may actually generate cost-savings while improving clinical outcomes and patient well-being. Further studies are clearly warranted to determine the optimal dose and schedule for Nanoxel as well as its comparative effectiveness to cremophor-based paclitaxel.

Multifunctional nanoparticles: cost versus benefit of adding targeting and imaging capabilities.

Nanoparticle-based drug delivery systems have been developed to improve the efficacy and reduce the systemic toxicity of a wide range of drugs. Although clinically approved nanoparticles have consistently shown value in reducing drug toxicity, their use has not always translated into improved clinical outcomes. This has led to the development of "multifunctional" nanoparticles, where additional capabilities like targeting and image contrast enhancement are added to the nanoparticles. However, additional functionality means additional synthetic steps and costs, more convoluted behavior and effects in vivo, and also greater regulatory hurdles. The trade-off between additional functionality and complexity is the subject of ongoing debate and the focus of this Review.