A new Eosin Y-based 'turnon' fluorescent sensor for ratiometric sensing of toxic mercury ion (Hg2+) offering unaided eye detection and its antibacterial activity.

A unique fluorescent molecule (ND-S) was obtained from Eosin Y in two simple yet high yielding steps (1). ND-S has special metal ion sensing ability, such that it can selectively detect toxic Hg2+ present in very low concentration in aqueous solutions in the presence of other competing metal ions. The host-guest complexation is ratiometric and is associated with significant increase in fluorescence during the process. Isothermal titration calorimetry (ITC) experiments provided thermodynamic parameters related to interaction between ND-S and Hg2+. Using inductively coupled plasma mass spectrometry (ICP-MS), the Hg2+(aq) removal efficiency of ND-S was estimated to be 99.88%. Appreciable limit of detection (LOD = 7.4 nM) was observed. Other competing ions did not interfere with the sensing of Hg2+ by ND-S. The effects of external stimuli (temperature and pH) were studied. Besides, the complex (ND-M), formed by 1:1 coordination of ND-S and Hg2+ was found to be effective against the survival of Gram-positive bacteria (S. aureus and B. subtilis) with a high selectivity index. Moreover, bacterial cell death mechanism was studied systematically. Overall, we have shown the transformation of a toxic species (Hg2+), extracted from polluted water by a biocompatible sensor (ND-S), into an effective and potent antibacterial agent (ND-M).

An updated landscape on nanotechnology-based drug delivery, immunotherapy, vaccinations, imaging, and biomarker detections for cancers: recent trends and future directions with clinical success.

The recent development of nanotechnology-based formulations improved the diagnostics and therapies for various diseases including cancer where lack of specificity, high cytotoxicity with various side effects, poor biocompatibility, and increasing cases of multi-drug resistance are the major limitations of existing chemotherapy. Nanoparticle-based drug delivery enhances the stability and bioavailability of many drugs, thereby increasing tissue penetration and targeted delivery with improved efficacy against the tumour cells. Easy surface functionalization and encapsulation properties allow various antigens and tumour cell lysates to be delivered in the form of nanovaccines with improved immune response. The nanoparticles (NPs) due to their smaller size and associated optical, physical, and mechanical properties have evolved as biosensors with high sensitivity and specificity for the detection of various markers including nucleic acids, protein/antigens, small metabolites, etc. This review gives, initially, a concise update on drug delivery using different nanoscale platforms like liposomes, dendrimers, polymeric & various metallic NPs, hydrogels, microneedles, nanofibres, nanoemulsions, etc. Drug delivery with recent technologies like quantum dots (QDs), carbon nanotubes (CNTs), protein, and upconverting NPs was updated, thereafter. We also summarized the recent progress in vaccination strategy, immunotherapy involving immune checkpoint inhibitors, and biomarker detection for various cancers based on nanoplatforms. At last, we gave a detailed picture of the current nanomedicines in clinical trials and their possible success along with the existing approved ones. In short, this review provides an updated complete landscape of applications of wide NP-based drug delivery, vaccinations, immunotherapy, biomarker detection & imaging for various cancers with a predicted future of nanomedicines that are in clinical trials.

Coal waste-derived synthesis of yellow oxidized graphene quantum dots with highly specific superoxide dismutase activity: characterization, kinetics, and biological studies.

The disintegration of coal-based precursors for the scalable production of nanozymes relies on the fate of solvothermal pyrolysis. Herein, we report a novel economic and scalable strategy to fabricate yellow luminescent graphene quantum dots (YGQDs) by remediating unburnt coal waste (CW). The YGQDs (size: 7-8 nm; M.W: 3157.9 Da) were produced using in situ "anion-radical" assisted bond cleavage in water (within 8 h; at 121 °C) with yields of ∼87%. The presence of exposed surface and edge groups, such as COOH, C-O-C, and O-H, as structural defects accounted for its high fluorescence with εmax ∼530 nm at pH 7. Besides, these defects also acted as radical stabilizers, demonstrating prominent anti-oxidative activity of ∼4.5-fold higher than standard ascorbic acid (AA). In addition, the YGQDs showed high biocompatibility towards mammalian cells, with 500 µM of treatment dose showing <15% cell death. The YGQDs demonstrated specific superoxide dismutase (SOD) activity wherein 15 µM YGQDs equalled the activity of 1-unit biological SOD (bSOD), measured using the pyrogallol assay. The Km for YGQDs was ∼10-fold higher than that for bSOD. However, the YGQDs retained their SOD activity in harsh conditions like high temperatures or denaturing reactions, where the activity of bSOD is completely lost. The binding affinity of YGQDs for superoxide ions, measured from isothermal calorimetry (ITC) studies, was only 10-fold lower than that of bSOD (Kd of 586 nM vs. 57.3 nM). Further, the pre-treatment of YGQDs (∼10-25 µM) increased the cell survivability to >75-90% in three cell lines during ROS-mediated cell death, with the highest survivability being shown for C6-cells. Next, the ROS-induced apoptosis in C6-cells (model for neurodegenerative diseases study), wherein YGQDs uptake was confirmed by confocal microscopy, showed ∼5-fold apoptosis alleviation with only 5 µM pretreatment. The YGQDs also restored the expression of pro-inflammatory Th1 cytokines (TNF-α, IFN-γ, IL-6) and anti-inflammatory Th2 cytokines (IL-10) to their basal levels, with a net >3-fold change observed. This further explains the molecular mechanism for the antioxidant property of YGQDs. The high specific SOD activity associated with YGQDs may provide the cheapest alternative source for producing large-scale SOD-based nanozymes that can treat various oxidative stress-linked disorders/diseases.

Immunoinformatics-based multi-epitope containing fused polypeptide vaccine design against visceral leishmaniasis with high immunogenicity and TLR binding.

Visceral leishmaniasis (VL) is the most lethal among all leishmaniasis diseases and remains categorized as a neglected tropical disease (NTD). This study aimed to develop a peptide-based multi-epitope vaccine construct against VL using immunoinformatics methodologies. To achieve this, four distinct proteins were screened to identify peptides consisting of 9-15 amino acids with high binding affinity to toll-like receptors (TLRs), strong antigenicity, low allergenicity, and minimal toxicity. The resulting multi-epitope vaccine construct was fused in a tandem arrangement with appropriate linker peptides and exhibited superior properties related to cytotoxic T lymphocytes (CTLs), helper T lymphocytes (HTLs), and B-cell epitopes. Subsequently, a three-dimensional (3D) model of the vaccine construct was generated, refined, and validated for structural stability and immune response capabilities. Molecular docking and simulations confirmed the vaccine construct's stability and binding affinities with TLRs, with TLR4 displaying the highest binding affinity, followed by TLR2 and TLR3. Additionally, simulations predicted robust cellular and humoral antibody-mediated immune responses elicited by the designed vaccine construct. Notably, this vaccine construct includes proteins from various pathways of Leishmania donovani (LD), which have not been previously utilized in VL vaccine design. Thus, this study opens new avenues for the development of vaccines against diverse protozoan diseases.

Dimensionality effects of g-C3N4 from wettability to solar light assisted self-cleaning and electrocatalytic oxygen evolution reaction.

Unique interfacial properties of 2D materials make them more functional than their bulk counterparts in a catalytic application. In the present study, bulk and 2D graphitic carbon nitride nanosheet (bulk g-C3N4 and 2D-g-C3N4 NS) coated cotton fabrics and nickel foam electrode interfaces have been applied for solar light-driven self-cleaning of methyl orange (MO) dye and electrocatalytic oxygen evolution reaction (OER), respectively. Compared to bulk, 2D-g-C3N4 coated interfaces show higher surface roughness (1.094 > 0.803) and enhanced hydrophilicity (θ âˆ¼ 32° < 62° for cotton fabric and θ âˆ¼ 25° < 54° for Ni foam substrate) due to oxygen defect induction as confirmed from morphological (HR-TEM and AFM) and interfacial (XPS) characterizations. The self-remediation efficiencies for blank and bulk/2D-g-C3N4 coated cotton fabrics are estimated through colorimetric absorbance and average intensity changes. The self-cleaning efficiency for 2D-g-C3N4 NS coated cotton fabric is 87%, whereas the blank and bulk-coated fabric show 31% and 52% efficiency. Liquid Chromatography-Mass Spectrometry (LC-MS) analysis determines the reaction intermediates for MO cleaning. 2D-g-C3N4 shows lower overpotential (108 mV) and onset potential (1.30 V) vs. RHE for 10 mA cm-2 OER current density in 0.1 M KOH. Also, the decreased charge transfer resistance (RCT = 12 Ω) and lower Tafel's slope (24 mV dec-1) of 2D-g-C3N4 make it the most efficient OER catalyst over bulk-g-C3N4 and state-of-the-art material RuO2. The pseudocapacitance behavior of OER governs the kinetics of electrode-electrolyte interaction through the electrical double layer (EDL) mechanism. The 2D electrocatalyst demonstrates long-term stability (retention ∼94%) and efficacy compared to commercial electrocatalysts.

Rationally Designed Ionic Covalent Organic Networks (iCONs) with Efficient Antimicrobial Activities.

Two unique ionic covalent organic networks (iCONs) incorporated with guanidinium motifs were obtained and characterized by various techniques. Upon 8 h of treatment with iCON-HCCP (250 µg/mL), >97% killing of Staphylococcus aureus, Candida albicans, and Candida glabrata strains was observed. Antimicrobial efficacies against bacteria and fungi were also evident from FE-SEM studies. High antifungal efficacies also correlated well with >60% reduction of ergosterol content, high lipid peroxidation, and membrane damage leading to necrosis.

Time-dependent exfoliation study of MoS2 for its use as a cathode material in high-performance hybrid supercapacitors.

Quick and precise exfoliation of bulk molybdenum sulphide into few layers can bring a quantum leap in the electrochemical performance of this material. Such a cost-effective exfoliation route to obtain few layers of MoS2 nanosheets with a high mass yield of ∼75% is presented in this study. The electrochemical behaviours of three types of samples, namely pristine MoS2 and MoS2 exfoliated for 3 h and 5 h, were compared and the reasons leading to their performance modulation are explained. The performance could be tuned by changing the nature of the electrolytes, as shown using three different electrolytes, i.e. H2SO4, Na2SO4, and KOH. The electrochemical performance of a supercapacitor device fabricated using the 5 h-exfoliated sample showed many fold improvement. The strategy of combining with a 2D material-based anode is an interesting way forward for such devices. In addition, the anode material has to be carefully chosen so that high performance can be ensured. The usefulness of 2D flake-like WO3 as an anode was investigated first before establishing its worthiness in a hybrid device. The hybrid device was able to deliver an excellent energy density of 33.74 W h kg-1 with long-term cycling stability and coulombic efficiency, thus proving its applicability for high-performance energy-storage devices.

An introduction to dynamic nucleoporins in Leishmania species: Novel targets for tropical-therapeutics.

As an ailment, leishmaniasis is still an incessant challenge in neglected tropical diseases and neglected infections of poverty worldwide. At present, the diagnosis and treatment to combat Leishmania tropical infections are not substantial remedies and require advanced & specific research. Therefore, there is a need for a potential novel target to overcome established medicament modalities' limitations in pathogenicity. In this review, we proposed a few ab initio findings in nucleoporins of nuclear pore complex in Leishmania sp. concerning other infectious protists. So, through structural analysis and dynamics studies, we hypothesize the nuclear pore molecular machinery & functionality. The gatekeepers Nups, export of mRNA, mitotic spindle formation are salient features in cellular mechanics and this is regulated by dynamic nucleoporins. Here, diverse studies suggest that Nup93/NIC96, Nup155/Nup144, Mlp1/Mlp2/Tpr of Leishmania Species can be a picked out marker for diagnostic, immune-modulation, and novel drug targets. In silico prediction of nucleoporin-functional interactors such as NUP54/57, RNA helicase, Ubiquitin-protein ligase, Exportin 1, putative T-lymphocyte triggering factor, and 9 uncharacterized proteins suggest few more noble targets. The novel drug targeting to importins/exportins of Leishmania sp. and defining mechanism of Leptomycin-B, SINE compounds, Curcumins, Selinexor can be an arc-light in therapeutics. The essence of the review in Leishmania's nucleoporins is to refocus our research on noble molecular targets for tropical therapeutics. Supplementary Information: The online version contains supplementary material available at 10.1007/s12639-022-01515-0.

The emerging role of Deubiquitinases (DUBs) in parasites: A foresight review.

Before the discovery of the proteasome complex, the lysosomes with acidic proteases and caspases in apoptotic pathways were thought to be the only pathways for the degradation of damaged, unfolded, and aged proteins. However, the discovery of 26S and 20S proteasome complexes in eukaryotes and microbes, respectively, established that the degradation of most proteins is a highly regulated ATP-dependent pathway that is significantly conserved across each domain of life. The proteasome is part of the ubiquitin-proteasome system (UPS), where the covalent tagging of a small molecule called ubiquitin (Ub) on the proteins marks its proteasomal degradation. The type and chain length of ubiquitination further determine whether a protein is designated for further roles in multi-cellular processes like DNA repair, trafficking, signal transduction, etc., or whether it will be degraded by the proteasome to recycle the peptides and amino acids. Deubiquitination, on the contrary, is the removal of ubiquitin from its substrate molecule or the conversion of polyubiquitin chains into monoubiquitin as a precursor to ubiquitin. Therefore, deubiquitylating enzymes (DUBs) can maintain the dynamic state of cellular ubiquitination by releasing conjugated ubiquitin from proteins and controlling many cellular pathways that are essential for their survival. Many DUBs are well characterized in the human system with potential drug targets in different cancers. Although, proteasome complex and UPS of parasites, like plasmodium and leishmania, were recently coined as multi-stage drug targets the role of DUBs is completely unexplored even though structural domains and functions of many of these parasite DUBs are conserved having high similarity even with its eukaryotic counterpart. This review summarizes the identification & characterization of different parasite DUBs based on in silico and a few functional studies among different phylogenetic classes of parasites including Metazoan (Schistosoma, Trichinella), Apicomplexan protozoans (Plasmodium, Toxoplasma, Eimeria, Cryptosporidium), Kinetoplastidie (Leishmania, Trypanosoma) and Microsporidia (Nosema). The identification of different homologs of parasite DUBs with structurally similar domains with eukaryotes, and the role of these DUBs alone or in combination with the 20S proteosome complex in regulating the parasite survival/death is further elaborated. We propose that small molecules/inhibitors of human DUBs can be potential antiparasitic agents due to their significant structural conservation.

Biomass derived self-assembled DNA-dot hydrogels for enhanced bacterial annihilation.

Nanotization of biomass for interesting biomedical applications is still in the nascent stage with no visible market available products. While products derived from biomass DNA and protein have unquestionable biocompatibility, induction of desired properties needs careful manipulation of the biomolecules. Herein, for the first time, we report the transformation of onion derived biomass DNA into DNA-dots through its partial hydrothermal pyrolysis to induce improved mechanical and photophysical properties. The DNA-dots were further used as crosslinkers to create a hydrogel through hybridization-mediated self-assembly with untransformed genomic DNA. The DNA dot-DNA hydrogel sustainably delivers the ciprofloxacin antibiotic as well as produces on-demand reactive oxygen species (ROS) with visible light irradiation. This prompted us to explore the hydrogel as a topical formulation for combination antibiotic Antibacterial-Photodynamic Therapy (APDT) applications. Remarkable annihilation of E. coli and S. aureus, and most importantly two drug-resistant strains of E. coli, shows the success of our sustainable approach.

Mechanistic insight into the role of mevalonate kinase by a natural fatty acid-mediated killing of Leishmania donovani.

We evaluated the anti-leishmanial efficacy of different saturated medium-chain fatty acids (FAs, C8-C18) where FA containing C8 chain, caprylic acid (CA), was found to be most potent against Leishmania donovani, the causative agent for visceral leishmaniasis (VL). Different analogs of CA with C8 linear chain, but not higher, along with a carboxyl/ester group showed a similar anti-leishmanial effect. Ergosterol depletion was the major cause of CA-mediated cell death. Molecular docking and molecular dynamic simulation studies indicated the enzyme mevalonate kinase (MevK) of the ergosterol biosynthesis pathway as a possible target of CA. Enzyme assays with purified recombinant MevK and CA/CA analogs confirmed the target with a competitive inhibition pattern. Using biochemical and biophysical studies; strong binding interaction between MevK and CA/CA analogs was established. Further, using parasites with overexpressed MevK and proteomics studies of CA-treated parasites the direct role of MevK as the target was validated. We established the mechanism of the antileishmanial effect of CA, a natural product, against VL where toxicity and drug resistance with current chemotherapeutics demand an alternative. This is the first report on the identification of an enzymatic target with kinetic parameters and mechanistic insights against any organism for a natural medium-chain FA.

In silico screening, molecular dynamic simulations, and in vitro activity of selected natural compounds as an inhibitor of Leishmania donovani 3-mercaptopyruvate sulfurtransferase.

In Leishmania sp., the enzymes of de novo cysteine biosynthesis pathway require sulfide. Other organisms utilize sulfide through the sulfide reduction pathway, but Leishmania lacks the gene that encodes these enzymes. Hence, the major source of sulfide for Leishmania is believed to be from the action of 3-mercaptopyruvate sulfurtransferase (3MST) on 3-mercapto-pyruvate (3MP). There has been no effort reported in the past to screen inhibitors against L. donovani 3MST (Ld3MST). As a result, this study examines natural compounds that are potent against Ld3MST and validates it by in vitro activity and cytotoxicity tests. Initially, a library of ~ 5000 natural compounds was subjected to molecular docking approach for screening, and the best hit was validated using a long-term molecular dynamic simulation (MD). Among the docking results, quercetine-3-rutinoside (Rutin) was deemed the best hit. The results of the MD indicated that Rutin was highly capable of interacting with the varied active site segments, possibly blocking substrate access. Additionally, promastigotes and amastigotes were tested for Rutin activity and the IC50 was found to be 40.95 and 90.09 µM, respectively. Similarly, the cytotoxicity assay revealed that Rutin was not toxic even at a concentration of 819.00 µM to THP-1 cell lines. Additionally, the Ld3MST was cloned, purified, and evaluated for enzyme activity in the presence of Rutin. Reduction in the enzyme activity (~ 85%) was observed in the presence of ~ 40 µM Rutin. Thus, this study suggests that Rutin may act as a potent inhibitor of Ld3MST. With further in vivo investigations, Rutin could be a small molecule of choice for combating leishmaniasis.

High-Performance, Nitrogen-Doped, Carbon-Nanotube-Based Electrochemical Sensor For Vitamin D3 Detection.

With the fast changing lifestyle, vitamin D deficiency is becoming extremely common. Therefore, development of economical, efficient, and fast sensors for vitamin D is the need of the hour. Carbon-based nanomaterials are extensively explored in sensing of variety of biomolecules. In the present study, an antibody-free, highly sensitive, carbon-nanotube-based, highly responsive vitamin D3 sensor is reported. Nitrogen-doped carbon nanotubes are utilized to overcome the limiting factor of hydrophobic character of pure carbon. The synthesized N-doped CNTs showed a specific surface area of 24 m2/g. The surface charges of vitamin D3 and the vitamin D3/NCNT complex are found to be -20 and -6.4 mV, respectively, by zeta potential measurements. The sensor is able to deliver high performance in the concentration range of 0-10 nM, with a limit of detection of 16 pM. The response study indicated the sensitivity value as 0.000495 mA/cm2 nM. The sensor is also able to show a higher selectivity toward vitamin D3 in comparison to other biomolecules. The long-term stability, reproducibility, good linear range, and ultralow detection capability of the sensor are also reported.

Carbon material produced by hydrothermal carbonisation of food waste as an electrode material for supercapacitor application: A circular economy approach.

This study aims to use landfill leachate (LL) as an aqueous medium during hydrothermal carbonisation (HTC) of food waste to produce hydrochar (FWH-LL-C), which could be used as an electrode material in energy storage devices. The structural properties and electrochemical performance of the hydrochar were compared to that obtained using distilled water as a reaction medium (FWH-DW-C). The results showed that there is a difference in Brunauer-Emmett-Teller (BET) surface area of FWH-LL-C (220 m2 gm-1) and FWH-DW-C (319 m2 gm-1). The electrochemical properties were comparable, with FWH-LL-C having 227 F g-1 specific capacitance at 1 A g-1 current density and FWH-DW-C having 235 F g-1 specific capacitance at 1 A g-1 current density. Furthermore, at a power density of 634 W kg-1, FWH-DW-C achieved the highest energy density of 14.4 Wh kg-1. The energy retention capacity of the electrode was 98% which indicate that the material has an excellent energy storage capacity. The findings suggested that LL could be used as an alternative source of aqueous media during the HTC of food waste to produce hydrochar which could be used as an effective electrode material in supercapacitors.

Limitations of current chemotherapy and future of nanoformulation-based AmB delivery for visceral leishmaniasis-An updated review.

Visceral leishmaniasis (VL) is the most lethal of all leishmaniasis diseasesand the second most common parasiticdisease after malaria and,still, categorized as a neglected tropical disease (NTD). According to the latest WHO study, >20 Leishmania species spread 0.7-1.0 million new cases of leishmaniasis each year. VL is caused by the genus, Leishmania donovani (LD), which affects between 50,000 and 90,000 people worldwide each year. Lack of new drug development, increasing drug resistance, toxicity and high cost even with the first line of treatmentof Amphotericin B (AmB), demands new formulation for treatment of VLFurther the lack of a vaccine, allowedthe researchers to develop nanofomulation-based AmB for improved delivery. The limitation of AmB is its kidney and liver toxicity which forced the development of costly liposomal AmB (AmBisome) nanoformulation. Success of AmBisome have inspired and attracted a wide range of AmB nanoformulations ranging from polymeric, solid lipid, liposomal/micellar, metallic, macrophage receptor-targetednanoparticles (NP) and even with sophisticated carbon/quantum dot-based AmBnano delivery systems. Notably, NP-based AmB delivery has shown increased efficacy due to increased uptake, on-target delivery and synergistic impact of NP and AmB. In this review, we have discussed the different forms of leishmaniasis disease and their current treatment options with limitations. The discovery, mechanism of action of AmB, clinical status of AmB and improvement with AmBisome over fungizone (AmB-deoxycholate)for VL treatment was further discussed. At last, the development of various AmB nanoformulation was discussed along with its adavantages over traditional chemotherapy-based delivery.

Microfluidic Platforms to Unravel Mysteries of Alzheimer's Disease: How Far Have We Come?

Alzheimer's disease (AD) is a significant health concern with enormous social and economic impact globally. The gradual deterioration of cognitive functions and irreversible neuronal losses are primary features of the disease. Even after decades of research, most therapeutic options are merely symptomatic, and drugs in clinical practice present numerous side effects. Lack of effective diagnostic techniques prevents the early prognosis of disease, resulting in a gradual deterioration in the quality of life. Furthermore, the mechanism of cognitive impairment and AD pathophysiology is poorly understood. Microfluidics exploits different microscale properties of fluids to mimic environments on microfluidic chip-like devices. These miniature multichambered devices can be used to grow cells and 3D tissues in vitro, analyze cell-to-cell communication, decipher the roles of neural cells such as microglia, and gain insights into AD pathophysiology. This review focuses on the applications and impact of microfluidics on AD research. We discuss the technical challenges and possible solutions provided by this new cutting-edge technique to understand disease-associated pathways and mechanisms.

7,8-dihydroxyflavone-functionalized gold nanoparticles target the arginase enzyme of Leishmania donovani.

Aim: To analyze the efficacy and possible mechanism of action of 7,8-dihydroxyflavone (DHF) and DHF synthesized gold nanoparticles (GNPs) against the parasite Leishmania donovani. Methods: GNPs were synthesized using DHF and characterized by dynamic light scattering, ζ potential, Fourier transform infrared spectroscopy, transmission electron microscopy and x-ray diffraction. The efficacy of DHF and DHF-GNP were tested against sensitive and drug-resistant parasites. GNP uptake was measured on macrophages by atomic absorption spectroscopy. Results: DHF and DHF-GNP (∼35 nm) were equally effective against sensitive and drug-resistant strains and inhibited the arginase activity of parasites. Increased IFN-γ and reduced IL-12 cytokine response showed a Th1/Th2-mediated cell death in macrophages. Conclusion: The low cytotoxicity and high biological activity of DHF-GNP may be useful for chemotherapy of leishmaniasis.

Current status of nanoscale drug delivery and the future of nano-vaccine development for leishmaniasis - A review.

The study of tropical diseases like leishmaniasis, a parasitic disease, has not received much attention even though it is the second-largest infectious disease after malaria. As per the WHO report, a total of 0.7-1.0 million new leishmaniasis cases, which are spread by 23 Leishmania species in more than 98 countries, are estimated with an alarming 26,000-65,000 death toll every year. Lack of potential vaccines along with the cost and toxicity of amphotericin B (AmB), the most common drug for the treatment of leishmaniasis, has raised the interest significantly for new formulations and drug delivery systems including nanoparticle-based delivery as anti-leishmanial agents. The size, shape, and high surface area to volume ratio of different NPs make them ideal for many biological applications. The delivery of drugs through liposome, polymeric, and solid-lipid NPs provides the advantage of high biocomatibilty of the carrier with reduced toxicity. Importantly, NP-based delivery has shown improved efficacy due to targeted delivery of the payload and synergistic action of NP and payload on the target. This review analyses the advantage of NP-based delivery over standard chemotherapy and natural product-based delivery system. The role of different physicochemical properties of a nanoscale delivery system is discussed. Further, different ways of nanoformulation delivery ranging from liposome, niosomes, polymeric, metallic, solid-lipid NPs were updated along with the possible mechanisms of action against the parasite. The status of current nano-vaccines and the future potential of NP-based vaccine are elaborated here.

Double proton transfer in a polar nano-droplet: Phototautomerization of alloxazine in AOT/alkane reverse micelles containing water or glycerol.

Alloxazine phototautomerization is believed to occur through an excited state double proton transfer (ESDPT) mechanism involving cyclic intermolecular H-bonded complexes between Alloxazine and hydroxylic solvents like water and alcohols. In AOT/alkane dispersions in the absence of any polar liquid, Alloxazine molecules reside inside the polar core of the AOT reverse micelle nanoparticles, where they involve in H-bonding with the anionic sulfonate head-groups of the AOT molecules, but are unable to generate the appropriate cyclic intermolecular H-bonded complexes conducive to ESDPT. However, tautomerization is switched on with addition of water and formation ofwater nano-droplet at the core of reverse micelle. Evidently, the Alloxazine⋅⋅⋅⋅AOT H-bonds are now replaced by Alloxazine⋅⋅⋅⋅Water H-bonds, promotingESDPT. On the other hand, Alloxazine phototautomerization is hindered in Glycerol, irrespective of whether the latter is in the bulk liquid state or in the form of a polar nano-droplet. This may be explained by steric considerations.