Nanomaterials as Novel Cardiovascular Theranostics

Cardiovascular diseases (CVDs) are a group of conditions associated with heart and blood vessels and are considered the leading cause of death globally. Coronary heart disease, atherosclerosis, myocardial infarction represents the CVDs. Since CVDs are associated with a series of pathophysiological conditions with an alarming mortality and morbidity rate, early diagnosis and appropriate therapeutic approaches are critical for saving patients’ lives. Conventionally, diagnostic tools are employed to detect disease conditions, whereas therapeutic drug candidates are administered to mitigate diseases. However, the advent of nanotechnological platforms has revolutionized the current understanding of pathophysiology and therapeutic measures. The concept of combinatorial therapy using both diagnosis and therapeutics through a single platform is known as theranostics. Nano-based theranostics are widely used in cancer detection and treatment, as evident from pre-clinical and clinical studies. Nanotheranostics have gained considerable attention for the efficient management of CVDs. The differential physicochemical properties of engineered nanoparticles have been exploited for early diagnosis and therapy of atherosclerosis, myocardial infarction and aneurysms. Herein, we provided the information on the evolution of nano-based theranostics to detect and treat CVDs such as atherosclerosis, myocardial infarction, and angiogenesis. The review also aims to provide novel avenues on how nanotherapeutics’ trending concept could transform our conventional diagnostic and therapeutic tools in the near future

Nanoparticle-Mediated Drug Delivery for the Treatment of Cardiovascular Diseases

Cardiovascular diseases (CVDs) are one of the foremost causes of high morbidity and mortality globally. Preventive, diagnostic, and treatment measures available for CVDs are not very useful, which demands promising alternative methods. Nanoscience and nanotechnology open a new window in the area of CVDs with an opportunity to achieve effective treatment, better prognosis, and less adverse effects on non-target tissues. The application of nanoparticles and nanocarriers in the area of cardiology has gathered much attention due to the properties such as passive and active targeting to the cardiac tissues, improved target specificity, and sensitivity. It has reported that more than 50% of CVDs can be treated effectively through the use of nanotechnology. The main goal of this review is to explore the recent advancements in nanoparticle-based cardiovascular drug carriers. This review also summarizes the difficulties associated with the conventional treatment modalities in comparison to the nanomedicine for CVDs

Chrysin‐Loaded Chitosan Nanoparticles Potentiates Antibiofilm Activity against \u3cem\u3eStaphylococcus aureus\u3c/em\u3e

The application of nanotechnology in medicine is gaining popularity due to its ability to increase the bioavailability and biosorption of numerous drugs. Chrysin, a flavone constituent of Orocylumineicum vent is well‐reported for its biological properties. However, its therapeutic potential has not been fully exploited due to its poor solubility and bioavailability. In the present study, chrysin was encapsulated into chitosan nanoparticles using TPP as a linker. The nanoparticles were characterized and investigated for their anti‐biofilm activity against Staphylococcus aureus. At sub‐Minimum Inhibitory Concentration, the nanoparticles exhibited enhanced anti‐biofilm efficacy against S. aureus as compared to its bulk counterparts, chrysin and chitosan. The decrease in the cell surface hydrophobicity and exopolysaccharide production indicated the inhibitory effect of the nanoparticles on the initial stages of biofilm development. The growth curve analysis revealed that at a sub‐MIC, the nanoparticles did not exert a bactericidal effect against S. aureus. The findings indicated the anti‐biofilm activity of the chrysin‐loaded chitosan nanoparticles and their potential application in combating infections associated with S. aureus

Isolation and Taxonomic Characterization of Novel Haloarchaeal Isolates From Indian Solar Saltern: A Brief Review on Distribution of Bacteriorhodopsins and V-Type ATPases in Haloarchaea

Haloarchaea inhabit high salinity environments worldwide. They are a potentially rich source of crucial biomolecules like carotenoids and industrially useful proteins. However, diversity in haloarchaea present in Indian high salinity environments is poorly studied. In the present study, we isolated 12 haloarchaeal strains from hypersaline Kottakuppam, Tamil Nadu solar saltern in India. 16S rRNA based taxonomic characterization of these isolates suggested that nine of them are novel strains that belong to genera Haloarcula, Halomicrobium, and Haloferax. Transmission electron microscopy suggests the polymorphic nature of these haloarchaeal isolates. Most of the haloarchaeal species are known to be high producers of carotenoids. We were able to isolate carotenoids from all these 12 isolates. The UV-Vis spectroscopy-based analysis suggests that bacterioruberin and lycopene are the major carotenoids produced by these isolates. Based on the visual inspection of the purified carotenoids, the isolates were classified into two broad categories i.e., yellow and orange, attributed to the differences in the ratio of bacterioruberin and lycopene as confirmed by the UV-Vis spectral analysis. Using a PCR-based screening assay, we were able to detect the presence of the bacteriorhodopsin gene (bop) in 11 isolates. We performed whole-genome sequencing for three bop positive and one bop negative haloarchaeal isolates. Whole-genome sequencing, followed by pan-genome analysis identified multiple unique genes involved in various biological functions. We also successfully cloned, expressed, and purified functional recombinant bacteriorhodopsin (BR) from one of the isolates using Escherichia coli as an expression host. BR has light-driven proton pumping activity resulting in the proton gradient across the membrane, which is utilized by V-Type ATPases to produce ATP. We analyzed the distribution of bop and other accessory genes involved in functional BR expression and ATP synthesis in all the representative haloarchaeal species. Our bioinformatics-based analysis of all the sequenced members of genus Haloarcula suggests that bop, if present, is usually inserted between the genes coding for B and D subunits of the V-type ATPases operon. This study provides new insights into the genomic variations in haloarchaea and reports expression of new BR variant having good expression in functional form in E. coli

Chrysin-Loaded Chitosan Nanoparticles Potentiates Antibiofilm Activity against Staphylococcus aureus

The application of nanotechnology in medicine is gaining popularity due to its ability to increase the bioavailability and biosorption of numerous drugs. Chrysin, a flavone constituent of Orocylumineicum vent is well-reported for its biological properties. However, its therapeutic potential has not been fully exploited due to its poor solubility and bioavailability. In the present study, chrysin was encapsulated into chitosan nanoparticles using TPP as a linker. The nanoparticles were characterized and investigated for their anti-biofilm activity against Staphylococcus aureus. At sub-Minimum Inhibitory Concentration, the nanoparticles exhibited enhanced anti-biofilm efficacy against S. aureus as compared to its bulk counterparts, chrysin and chitosan. The decrease in the cell surface hydrophobicity and exopolysaccharide production indicated the inhibitory effect of the nanoparticles on the initial stages of biofilm development. The growth curve analysis revealed that at a sub-MIC, the nanoparticles did not exert a bactericidal effect against S. aureus. The findings indicated the anti-biofilm activity of the chrysin-loaded chitosan nanoparticles and their potential application in combating infections associated with S. aureus

Nanomaterials as Novel Cardiovascular Theranostics

Cardiovascular diseases (CVDs) are a group of conditions associated with heart and blood vessels and are considered the leading cause of death globally. Coronary heart disease, atherosclerosis, myocardial infarction represents the CVDs. Since CVDs are associated with a series of pathophysiological conditions with an alarming mortality and morbidity rate, early diagnosis and appropriate therapeutic approaches are critical for saving patients’ lives. Conventionally, diagnostic tools are employed to detect disease conditions, whereas therapeutic drug candidates are administered to mitigate diseases. However, the advent of nanotechnological platforms has revolutionized the current understanding of pathophysiology and therapeutic measures. The concept of combinatorial therapy using both diagnosis and therapeutics through a single platform is known as theranostics. Nano-based theranostics are widely used in cancer detection and treatment, as evident from pre-clinical and clinical studies. Nanotheranostics have gained considerable attention for the efficient management of CVDs. The differential physicochemical properties of engineered nanoparticles have been exploited for early diagnosis and therapy of atherosclerosis, myocardial infarction and aneurysms. Herein, we provided the information on the evolution of nano-based theranostics to detect and treat CVDs such as atherosclerosis, myocardial infarction, and angiogenesis. The review also aims to provide novel avenues on how nanotherapeutics’ trending concept could transform our conventional diagnostic and therapeutic tools in the near future

Antioxidant and Anti-infective Potential of Ethanolic Extract of Eriobotrya bengalensis (Roxb.) Hook. f.: Phytochemicals Investigation and Molecular Docking Studies

In India, north-east region holds a special position of having diverse range of plants belonging to endemic species with widespread ethnomedicinal properties which remain unexplored till date. In the present study, Eriobotrya bengalensis (Roxb.) Hook. f. extract was evaluated for its radical scavenging activity and ability to combat quorum sensing regulated bacterial virulence in Pseudomonas aeruginosa PAO1. The ethanolic leaf extract of E. bengalensis (Roxb.) Hook. f. exhibited a concentration dependent radical scavenging of highly reactive DPPH and hydroxyl radicals with a scavenging percentage of 76.84 ± 4.72 and 67.37 ± 4.35 % respectively at a concentration of 500 µg/ml. E. bengalensis (Roxb.) Hook. f. also showed significant reducing power and relatively high ascorbic acid equivalent. The plant extract was also evaluated for its ability to down-regulate the production of quorum sensing (QS) regulated pathogenic determinants in P. aeruginosa PAO1. The violacein production in Chromobacterium violaceum and pyocyanin production in P. aeruginosa PAO1 was greatly inhibited on treatment with sub-MIC of E. bengalensis (Roxb.) Hook. f. with an inhibition of 79.58 ± 4.13 and 76.31 ± 4.03 % respectively. The anti-biofilm activity was further confirmed by confocal laser scanning microscopic (CLSM) analysis. The anti QS activity of E. bengalensis (Roxb.) Hook. f. was further corroborated by molecular docking studies which provides an insight into the mechanism of QS inhibition. The present result will provide novel leads to the application of unexplored plant species towards the development of novel anti-infectives in the post-antibiotic era

Methanolic Extract of Plectranthus tenuiflorus Attenuates Quorum Sensing Mediated Virulence and Biofilm Formation in Pseudomonas aeruginosa PAO1

Pseudomonas aeruginosa is an important opportunistic pathogen which causes bacterial keratitis, cyctic fibrosis and other hospital acquired infections. Its ability to form biofilm provides resistance to conventional antibiotics and further corroborates the global health concerns. The antibiotic resistance by P. aeruginosa is due to highly complex cellular signaling system called quorum sensing (QS). As QS controls bacterial pathogenicity and plays a crucial role in biofilm formation, it is a promising alternative target to combat the bacterial virulence. The present study aims to determine the inhibitory activity of Plectranthus tenuiflorus extract on QS and biofilm development in P. aeruginosa PAO1. The crude plant extract inhibited the production of pyocyanin, elastase, protease and chitinase by 71.96 ± 1.82, 38.74 ± 1.29, 30.84 ± 1.20 and 44.75 ± 1.40 % respectively at sub-MIC concentration of 500 µg/ml. The production of biofilm aggravating phenotypes such as exopolysaccharides, alginate and rhamnolipid were also significantly reduced. The biofilm inhibition capability of P. tenuiflorus was further supported by light microscopic and confocal laser scanning microscopic analysis. The phytochemicals such as phytol and mosloflavone were identified from the crude extract using gas chromatography–mass spectrometry (GC-MS). The role of these phytochemicals in down regulation of QS in P. aeruginosa was further confirmed by in silico studies targeting transcriptional receptors, LasR and RhlR of the QS regulatory network. The in vitro and docking studies suggest the anti QS potential of P. tenuiflorus in combating the bacterial pathogenesis

Biosynthesis of Silver Chloride Nanoparticles (AgCl-NPs) from Extreme Halophiles and Evaluation of Their Biological Applications

The biosynthesis of nanoparticles (NPs) has gained an overwhelming interest due to their biological applications. However, NPs synthesis by pigmented extreme halophiles remains underexplored. The NPs synthesis using pigmented halophiles is inexpensive and less toxic than other processes. In this study, pigmented halophilic microorganisms (n = 77) were screened to synthesize silver chloride nanoparticles (AgCl-NPs) with silver nitrate as metal precursors, and their biological applications were assessed. The synthesis of AgCl-NPs was possible using the crude extract from cellular lysis (CECL) of six extreme halophiles. Two of the AgCl-NPs viz. AK2-NPs and MY6-NPs synthesized by the CECL of Haloferax alexandrinus RK_AK2 and Haloferax lucentense RK_MY6, respectively, exhibited antimicrobial, antioxidative, and anti-inflammatory activities. The surface plasmon resonance of the AgCl-NPs was determined with UV spectroscopy. XRD analysis of AK2-NPs and MY6-NPs confirmed the presence of silver in the form of chlorargyrite (silver chloride) having a cubic structure. The crystallite size of AK2-NPs and MY6-NPs, estimated with the Scherrer formula, was 115.81 nm and 137.50 nm. FTIR analysis verified the presence of diverse functional groups. Dynamic light-scattering analysis confirmed that the average size distribution of NPs was 71.02 nm and 117.36 nm for AK2-NPs and MY6-NPs, respectively, with monodisperse nature. The functional group in 1623–1641 cm−1 indicated the presence of protein β-sheet structure and shifting of amino and hydroxyl groups from the pigmented CECL, which helps in capping and stabilizing nanoparticles. The study provides evidence that CECL of Haloferax species can rapidly synthesize NPs with unique characteristics and biological applications.This work was the partial financial support from DST-EMR (2016/003715/BBM), SERB-EMEQ/051/2014, and EEQ/2018/001085