Mixed oxide nanotubes in nanomedicine: A dead-end or a bridge to the future?

Nanomedicine has seen a significant rise in the development of new research tools and clinically functional devices. In this regard, significant advances and new commercial applications are expected in the pharmaceutical and orthopedic industries. For advanced orthopedic implant technologies, appropriate nanoscale surface modifications are highly effective strategies and are widely studied in the literature for improving implant performance. It is well-established that implants with nanotubular surfaces show a drastic improvement in new bone creation and gene expression compared to implants without nanotopography. Nevertheless, the scientific and clinical understanding of mixed oxide nanotubes (MONs) and their potential applications, especially in biomedical applications are still in the early stages of development. This review aims to establish a credible platform for the current and future roles of MONs in nanomedicine, particularly in advanced orthopedic implants. We first introduce the concept of MONs and then discuss the preparation strategies. This is followed by a review of the recent advancement of MONs in biomedical applications, including mineralization abilities, biocompatibility, antibacterial activity, cell culture, and animal testing, as well as clinical possibilities. To conclude, we propose that the combination of nanotubular surface modification with incorporating sensor allows clinicians to precisely record patient data as a critical contributor to evidence-based medicine.

Biosynthesis of Silver Nanoparticles From Marine Actinobacterium Micromonospora sp. and Their Bioactive Potential.

Background The biosynthesis of nanoparticles represents a rapid, environmentally friendly, cost-effective, and straightforward technology. This approach allows for the production of nanoparticles with a wide range of chemical compositions, sizes, shapes, high uniformity, and scalability. One of the principal advantages of biogenic nanoparticles is their water solubility and compatibility with biological systems. Biologically synthesized nanoparticles have demonstrated superior efficiency compared to conventionally synthesized particles. Among biosynthesis, microbial-mediated biosynthesis is a promising one that has a selectively reducing ability on specific metal ions through electron transfer.  Objectives Evaluation of antimicrobial and antioxidant activity of silver nanoparticle synthesized by actinobacteria Micromonospora sp. which is isolated from marine environment. Materials and methods In this study, actinobacteria were isolated from the marine sediment using the spread plate method. The isolates were identified based on morphological observation, cell wall amino acids, sugar analysis, and micromorphological analysis. The silver nanoparticle synthesis from microbes and their inhibition against clinical pathogens have been evaluated by the disc diffusion method. Antioxidant efficiency was evaluated in terms of total antioxidant activity through ammonium molybdenum assay. Results A total of five isolates were isolated from the sediment sample. The cell-free extract of MBIT-MSA4 can synthesize silver nanoparticles that have potential antimicrobial activity against the clinical pathogens Streptococcus mutans at a zone of inhibition 6 mm, 10 mm inhibition zone of Klebsiella pneumonia, and 8 mm zone of inhibition of Staphylococcus aureus. Also, it has significant antioxidant activity up to 73% of free radical inhibition. Conclusion Marine microbial-mediated biosynthesized silver nanoparticles have potential antimicrobial activity against S. mutans and methicillin-resistant Staphylococcus aureus (MRSA) and inhibit the oxidation process through antioxidant activity. This enhanced efficient biosynthesised nanoparticle has significantly reduced the concentration of free radicals caused by pathogens.

Reduction in the COVID-19 pneumonia case fatality rate by silver nanoparticles: A randomized case study.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has devastated mankind. To date, no approved treatment is available to completely combat this disease. Although many studies reported the potential of silver nanoparticles' (AgNPs) action mechanism and effect against SARS-CoV-2, this is the first clinical trial that aimed to prove this effect. This open-label, randomized, parallel-group, investigator-initiated study (IIS) was conducted in India from 2021 to 2022 and included 40 patients diagnosed with moderately-severe to severe COVID-19 pneumonia. This study proved a significantly higher survival rates (p < 0.05) and significantly lower number of days until supplemental oxygenation was required (p < 0.0001) for patients receiving intravenous AgNPs in form of AgSept® in addition to the standard COVID-19 treatment. This study highlights the importance of intravenous AgNPs administration in the treatment of virus-induced pneumonia.

Roles and current applications of S-nitrosoglutathione in anti-infective biomaterials.

Bacterial infections can compromise the physical and biological functionalities of humans and pose a huge economical and psychological burden on infected patients. Nitric oxide (NO) is a broad-spectrum antimicrobial agent, whose mechanism of action is not affected by bacterial resistance. S-nitrosoglutathione (GSNO), an endogenous donor and carrier of NO, has gained increasing attention because of its potent antibacterial activity and efficient biocompatibility. Significant breakthroughs have been made in the application of GSNO in biomaterials. This review is based on the existing evidence that comprehensively summarizes the progress of antimicrobial GSNO applications focusing on their anti-infective performance, underlying antibacterial mechanisms, and application in anti-infective biomaterials. We provide an accurate overview of the roles and applications of GSNO in antibacterial biomaterials and shed new light on the avenues for future studies.

Biosynthesis of silver nanoparticles using Malva parviflora and their antifungal activity.

Cheeseweed mallow (Malva parviflora L.) was used to biosynthesize silver nanoparticles. The biosynthesized silver nanoparticles were classified by UV-vis Spectroscopy and Fourier-Transform Infrared Spectroscopy (FT-IR). The shape and size distribution were visualized by Transmission Electron Microscopy (TEM), Field Emission Scanning Electron Microscopy (FE-SEM), and Zeta potential analysis. The chemical composition of M. parviflora leaf extract was identified by Gas Chromatography and Mass Spectroscopy (GC/MS). Finally, in vitro antifungal assay was done to assess the potential of biosynthesized silver nanoparticles and crude leaf extract of M. parviflora for inhibiting the mycelial growth of phytopathogenic fungi. The UV-vis analysis manifests the formation of silver nanoparticles. FTIR analysis established that chemicals of the leaf extract stabilized the biosynthesized silver nanoparticles by binding with the free silver ions. The TEM, FE-SEM and zeta potential analyzer confirmed that the biosynthesized silver nanoparticles were mostly spherical with an average diameter of 50.6 nm. The biosynthesized silver nanoparticles and leaf extract of M. parviflora effectively mitigate the mycelial growth of Helminthosporium rostratum, Fusarium solani, Fusarium oxysporum, and Alternaria alternata. The maximum reduction in mycelial growth by biosynthesized nanoparticles was observed against H. rostratum (88.6%). Whereas, the leaf extract of M. parviflora was most effective against F. solani (65.3%). Thus, the biosynthesis of nanoparticle assisted by M. parviflora is a feasible and eco-friendly method for the synthesis of silver nanoparticles. Further the silver nanoparticles and leaf extract of M. parviflora could be explored for the development of the fungicide.

Toxicity of colloidal silver products and their marketing claims in Finland.

AIMS: The aim was to investigate the marketing practices, beliefs and health claims regarding the use of colloidal silver in Finland. Silver nanoparticles (AgNPs) are potentially toxic due to their small size and Ag+-release capabilities, and the use of colloidal silver products containing AgNPs can cause a wide variety of adverse effects such as argyria. METHODS: Contents of three company websites selling colloidal silver were reviewed, and the claims used in the marketing of colloidal silver were compared to the scientific information about silver. In Facebook posts and discussion about colloidal silver were analyzed. RESULTS: In Finland, the marketing of colloidal silver products on websites selling the products did not follow the regulations of authorities; several scientifically unfounded claims about the efficacy and medical use of colloidal silver were found. After the Finnish Broadcasting Company (Yle) documentary and an intervention by authorities, contents of the websites were changed, but still questionable information and misleading claims could be found. In the analyzed Facebook groups attitudes towards medical use of colloidal silver were uncritically positive, internal use was highly promoted and the restrictions of use were considered unjustified. CONCLUSIONS: The use of quackery products such as colloidal silver can be dangerous, and their use and marketing should be controlled and restricted.

Amelioration of diethylnitrosamine (DEN) induced renal oxidative stress and inflammation by Carissa carandas embedded silver nanoparticles in rodents.

INTRODUCTION: Inflammation and oxidative stress are the main factors ascribed with interruption in the process of renal tissue impairment. The toxicity of different types of nitrosamine is well recognized in animals and humans. Administration of the smallest quantities of diethylnitrosamine or dimethylnitrosamine either orally or parenterally results into renal damage. Therapeutic effects of phytofabricated silver nanoparticles of Carissa carandas aqueous extract has been scrutinised in current study for the assessment of renal cancer activity in animal model. METHODOLOGY: Phytofabricated silver nanoparticles were characterized by using different instrumentation. Nephroprotective activity of silver nanoparticles at different doses was evaluated against N-diethylnitrosamine (200 mg/kg b.w., intraperitoneal) in animal model. Serum and renal homogenate were taken to evaluate the renal toxicity markers, oxidative stress, and antioxidant parameter, proinflammatory cytokines and histopathological study. RESULT: Significant outcomes of silver nanoparticles in dose dependent manner down regulated the elevated serum marker, tumour marker enzymes and histopathology observation of repaired tissue assured the renal cancer activity in animals. In addition, profile of enzymatic and non-enzymatic antioxidant, proinflammatory cytokines and tumour promotion marker also favours the anticancer property of silver nanoparticles. CONCLUSION: The data of current study reveals silver nanoparticles ameliorates renal oxidative stress and carcinogenesis which was induced by N-diethylnitrosamine and accredited to antioxidant and anticancer activities of phytofabricated nanoparticles by biological approach.

A versatile tool in controlling aggregation and Ag nanoparticles assisted in vitro folding of thermally denatured zDHFR.

BACKGROUND: Proteins have tendency to form inactive aggregates at higher temperatures due to thermal instability. Maintenance of thermal stability is essential to gain the protein in sufficient quantity and biologically active form during their commercial production. METHODS: BL21-DE3 Rosetta E. coli cells which contains plasmid pET43.1a vector was used for producing zDHFR protein commercially. The purification of N-terminal Histidine tagged zDHFR was performed by Immobilized Metal Ion chromatography (IMAC). Investigations were performed in existence and non existence of Silver nanoparticles (AgNPs). The inactivation kinetics of zDHFR in existence and non existence of AgNPs were monitored over a range of 40-80 °C as monitored by UV-Visible absorption spectroscopy. RESULTS: The protein completely lost its activity at 55 °C. Kinetics of inactivated zDHFR follows first order model in presence and absence of AgNPs. Decrease in rate constant (k) values at respective temperatures depicts that AgNPs contribute in the thermostability of the protein. AgNPs also assists in regaining the activity of zDHFR protein. CONCLUSIONS: AgNPs helps in maintaining thermostability and reducing the aggregation propensity of zDHFR protein. GENERAL SIGNIFICANCE: Result explains that AgNPs are recommended as a valuable system in enhancing the industrial production of biologically active zDHFR protein which is an important component in folate cycle and essential for survival of cells and prevents the protein from being aggregated.

Induction of intrinsic apoptotic signaling pathway in A549 lung cancer cells using silver nanoparticles from Gossypium hirsutum and evaluation of in vivo toxicity.

In the past decade, the research communities raised wide concerns on using medicinal plants for synthesis of nanomaterials due to its effective biological activity, lower side effects and also eco-friendly manner. Our previous report concentrated on the biomedical efficacy of fine characterized silver nanoparticles (AgNPs) from Gossypium hirsutum (cotton) leaf extract. Further, the current examination is planned to reveal the molecular mechanisms involving for activation of mitochondria-mediated signaling pathway by AgNPs in human lung cancer cells (A549) using various biological endpoints such as apoptotic induction by HOECHST 33342, AO/EtBr and Rhodamine 123 staining, cell cycle analysis using flow cytometry, gene and protein expressions by RT-PCR and immunoblotting respectively. This study was further extended to identify the toxicity of AgNPs using an animal model. Interestingly, we observed that A549 cells treated with AgNPs resulted in G2/M arrest and ultimately leads to induction of apoptosis cell death. Moreover, gene analysis demonstrated that diminished expression of anti-apoptotic (Bcl-2) and enhanced expression of pro-apoptotic (Bax) mitochondrial genes. The alterations in the gene pattern may interrupt of mitochondrial membrane potential which facilitates the releasing of cytochrome c (cyt c) into cytosol. The cyt c act as a key molecule for activation of caspases (9 and 3) to initiate intrinsic apoptotic signaling cell death process. The histological analysis proven the application of AgNPs in nanomedicine is quietly harmless and would not cause any discernible stress like swelling and inflammation to the organs of mice. Taken together, this investigation may provide solid evidence for cotton crop mediated AgNPs induced apoptosis cell death pathway and offer a novel approach for cancer therapy.

Data in support of Gallium (Ga(3+)) antibacterial activities to counteract E. coli and S. epidermidis biofilm formation onto pro-osteointegrative titanium surfaces.

This paper contains original data supporting the antibacterial activities of Gallium (Ga(3+))-doped pro-osteointegrative titanium alloys, obtained via Anodic Spark Deposition (ASD), as described in "The effect of silver or gallium doped titanium against the multidrug resistant Acinetobacter baumannii" (Cochis et al. 2016) [1]. In this article we included an indirect cytocompatibility evaluation towards Saos2 human osteoblasts and extended the microbial evaluation of the Ga(3+) enriched titanium surfaces against the biofilm former Escherichia coli and Staphylococcus epidermidis strains. Cell viability was assayed by the Alamar Blue test, while bacterial viability was evaluated by the metabolic colorimetric 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. Finally biofilm morphology was analyzed by Scanning Electron Microscopy (SEM). Data regarding Ga(3+) activity were compared to Silver.

Short-term changes in intracellular ROS localisation after the silver nanoparticles exposure depending on particle size.

Silver nanoparticles (AgNPs) induce the production of reactive oxygen species (ROS) and apoptosis. These effects are enhanced by smaller particles. Using live-cell imaging, we show that AgNPs induced ROS production rapidly in a size-dependent manner after exposure of cells to 70-nm and 1-nm AgNPs (AgNPs-70, AgNPs-1), but not AgNO3. Exposure of cells to 5 µg/mL each of AgNPs-70, AgNPs-1 or AgNO3 for 1 h decreased the cell viability by approximately 40%, 100% and 20%, respectively. ROS were rapidly induced after 5 and 60 min by AgNPs-1 and AgNPs-70, respectively, whereas AgNO3 had no detectable effect. ROS production detected using the reporter dichlorodihydrofluorescein was observed in whole cells and mitochondria 5 and 60 min after exposure to AgNPs-1. The present study is the first, to our knowledge, to report the temporal expression and intracellular localisation of ROS induced by AgNPs.