Dual stimuli-responsive and sustained drug delivery NanoSensoGel formulation for prevention of cisplatin-induced ototoxicity.

Cisplatin (CisPt)-induced ototoxicity (CIO) is delineated as a consequence of CisPt-induced intracellular generation of reactive oxygen species (ROS) which can be circumvented by Bucillamine (BUC; an antioxidant drug with sulfhydryl groups) and Diltiazem (DLT, L-type calcium channel blocker). However, its effective accumulation in the Organ of Corti and cell cytoplasm is desired. Therefore, a biocompatible BUC- and DLT-nanoparticles (NPs)-impregnated dual stimuli-responsive formulation (NanoSensoGel) presented here with ROS- and thermo-responsive properties for the sustained and receptive delivery of drugs. The ROS-responsive polypropylene sulfide- methyl polyethylene glycol-2000 (PPS-mPEG2000) polymer was rationally designed, synthesized, and characterized to fabricate BUC- and DLT-loaded PPS-mPEG2000-NPs (BUC- and DLT-NPs). The fabricated BUC- and DLT-NPs showed efficient cellular uptake, intracellular delivery, ROS responsiveness, and cytoprotective effect which was characterized using cellular internalization, intracellular ROS, mitochondrial superoxide, and Caspase 3/7 assays on the House Ear Institute-Organ of Corti-1 (HEI-OC1) cells. The composite NanoSensoGel (i.e., ROS-responsive BUC- and DLT-NPs suspended in the thermo-responsive hydrogel) present in a sol state at room temperature and turned to gel above 33°C, which could be essential for retaining the formulation at the target site for long-term release. The NanoSensoGel showed sustained release of BUC and DLT following Fickian release diffusion kinetics. Overall, a novel NanoSensoGel formulation developed in this study has demonstrated its great potential in delivering therapeutics in the inner ear for prophylactic treatment of CIO, and associated hearing loss.

Antioxidant supplementation during treatment of outpatient dogs with parvovirus enteritis ameliorates oxidative stress and attenuates intestinal injury: A randomized controlled trial.

A prospective randomized controlled clinical study was conducted to determine whether antioxidant supplementation as an adjunct therapy alters hemogram, oxidative stress, serum intestinal fatty acid binding protein-2 (IFABP-2) level, fecal viral load, clinical score (CS) and survivability in outpatient canine parvovirus enteritis (CPVE) dogs. The dogs with CPVE were randomized to one of the five treatment groups: supportive treatment (ST) alone, ST with N-acetylcysteine (ST+NAC), resveratrol (ST+RES), coenzyme Q10 (ST+CoQ10) or ascorbic acid (ST+AA). The primary outcome measures were reduction of CS and fecal HA titre, and enhancement of survivability. Secondary outcome measures were reduction of oxidative stress indices and IFABP-2 level from day 0 to day 7. The mean CS and HA titre were significantly (P < 0.05) decreased from day 0 to 7 in ST and all antioxidant groups. The supplementations of NAC, RES and AA along with ST markedly (P < 0.05) reduced the concentrations of malondialdehyde, nitric oxide and IFABP-2 on day 7 as compared to ST alone. Additionally, NAC and RES supplementations markedly (P < 0.05) improved the total leukocyte count and neutrophil count in CPVE-affected dogs. NAC and RES could serve as better antioxidants for the amelioration of oxidative stress in CPVE but, the antioxidants did not confer any additional benefits in reduction of CS, fecal HA tire, or survivability when compared with ST alone.

Cucumis callosus (Rottl.) Cogn. fruit extract ameliorates calcium oxalate urolithiasis in ethylene glycol induced hyperoxaluric Rat model.

Cucumis callosus dry fruits are traditionally used as folk remedy to treat conditions like urethral irritations, urine stoppage or dribbling and other urinary ailments of man in north-west India. But no study is reported to validate this ethnic practice of using Cucumis fruit in urolithiasis. To evaluate anti-urolithiatic potential of Cucumis, hyperoxaluria was induced in rats by supplying 0.75% ethylene glycol (EG) + 1% ammonium chloride (AC) in drinking water for 14 days. Anti-urolithiatic activity of Cucumis callosus hydro-ethanolic extract (CCHEE) was assessed by measuring blood and urine biochemical parameters, oxidative stress indices, histopathology and osteopontin (OPN) expression. Administration of EG-AC to rats caused hyperoxaluria, crystalluria, azotaemia, oxidant/antioxidant imbalance (increase in lipid peroxidation (LPO), and decrease in glutathione (GSH) and catalase (CAT)), up-regulation of OPN and calcium oxalate (CaOx) crystal deposition in kidney. Treatment of afflicted rats with Cucumis fruits extract restored renal function to a great extent (CCHEE group), testified by improvement of stated parameters. Findings demonstrate curative efficacy of Cucumis fruit extract in EG induced urolithiasis of rats. The restoration of renal function was possibly by regulating renal stone formation via reducing urinary oxalate excretion, correcting oxidant/antioxidant imbalances, and reduced expression of OPN. Hence, results of this study validate the ethnic practice of using Cucumis fruit and conclude that fruit extracts have beneficial effects on CaOx urolithiasis and renal function.

Naturally occurring Anaplasma marginale infection in cattle: Molecular prevalence and associated risk factors, haemato-biochemical alterations, oxidant/antioxidant status and serum trace mineral levels.

The present investigation was undertaken to map the distribution of Anapalsma species infection in cattle from the Aizawl region of Mizoram, India, in relation to various risk factors, and to study the haemato-biochemical alterations, oxidant/antioxidant status and serum trace mineral levels in cattle with naturally occurring Anapalsma marginale infection. The study was carried out over 31 months from June 2019 to December 2021. A total of 401 cattle blood samples were collected and screened for the presence of Anaplasma spp. by microscopic examination and polymerase chain reaction (PCR). Non-infected clinically healthy cattle (n = 21) served as control. Blood samples were collected to study the haemogram and serum samples were used for the evaluation of biochemical parameters, oxidative stress indices and trace minerals. During the study period, an overall prevalence of 15.71% was recorded for A. marginale infection in cattle. The prevalence of A. marginale infection was highly associated with age, sex, breed and tick infestation status of animals, floor system and management of farms, and season. The mean values of total erythrocyte count (TEC), haemoglobin (Hb), packed cell volume (PCV), total platelet count, total protein, albumin, superoxide dismutase (SOD), glutathione (GSH), total antioxidant capacity (TAC), copper (Cu) and zinc (Zn) were significantly (P < 0.05) lower, whereas the mean values of mean corpuscular volume (MCV), aspartate aminotransferase (AST), total bilirubin, indirect bilirubin, blood urea nitrogen (BUN), creatinine and lipid hydroperoxide (LPO) were significantly (P < 0.05) higher in cattle infected with A. marginale. A negative correlation of TEC with LPO, and a positive correlation with SOD, GSH, TAC, Cu and Zn suggest a possible link between oxidative stress and the haemolytic crisis noticed in bovine anaplasmosis. Incorporation of antioxidants and organ protective drugs as an adjunct therapy may result in better prognosis.

A 5-Year Prospective Study on Incidence and Clinico-pathological Changes Associated with Naturally Occurring Trypanosomosis in Dogs of Mizoram, India.

PURPOSE: The present research was taken to study the hospital-based incidence and clinico-pathological changes associated with naturally occurring trypanosomosis in dogs of Mizoram. METHODS: A 5-year prospective study on hospital-based incidence and clinico-pathological changes associated with naturally occurring trypanosomosis in dogs of Mizoram was carried out during the study period from April, 2015 to March, 2020. Trypanosoma evansi infection was confirmed by microscopic examination and polymerase chain reaction (PCR). Non-infected clinically healthy dogs (n = 6) served as control. Blood samples were collected to study the haemogram and serum samples were used for the evaluation of serum biochemical parameters and oxidant-antioxidant parameters. RESULTS: During the study period, an overall incidence of 0.25% was recorded for trypanosomosis in dogs. The most consistent clinical findings noticed were anorexia/inappetence, pyrexia, depression/lethargy, pale mucous membrane, dehydration and lymphadenomegaly. Anaemia, granulocytopenia, lymphocytosis and thrombocytopenia were the major findings noticed in trypanosomosis affected dogs. The profile of vital organ function revealed that the mean values of total protein, albumin and random blood glucose were significantly (P < 0.05) lower, whereas the mean values of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin, blood urea nitrogen (BUN) and creatinine were significantly (P < 0.05) higher in dogs affected with trypanosomosis. The mean value of lipid hydroperoxide (LPO) was significantly (P < 0.05) higher, whereas the mean values of glutathione (GSH), superoxide dismutase (SOD) and total antioxidant activity (TAOA) were significantly (P < 0.05) lower in trypanosomosis affected dogs. When total erythrocyte count (TEC) was correlated with LPO (r = - 0.631, P < 0.05), a negative correlation was found, while in case of GSH (r = 0.757, P < 0.05), SOD (r = 0.767, P < 0.05) and TAOA (r = 0.713, P < 0.05), it was positively correlated. CONCLUSION: A negative correlation of TEC count with LPO, while a positive correlation with GSH, SOD and TAOA signify the role of oxidative stress in the pathogenesis of anaemia induced by T. evansi infection in dogs. The present study findings might be helpful to clinicians when treating clinical cases of this kind. Incorporation of organ protective drugs and antioxidants in the treatment schedule may result in better prognosis.

Light-assisted anticancer photodynamic therapy using porphyrin-doped nanoencapsulates.

Light activatable porphyrinic photosensitizers (PSs) are essential components of anticancer and antimicrobial therapy and diagnostic imaging. However, their biological applications are quite challenging due to the lack of hydrophilicity and biocompatibility. To overcome such drawbacks, photosensitizers can be doped into a biocompatible polymer such as gelatin and further can be used for biomedical applications. Herein, first, a novel A4 type porphyrin PS [5,10,15,20-tetrakis(4-pyridylamidephenyl)porphyrin; TPyAPP] was synthesized via a rational route with good yield. Further, this porphyrin was encapsulated into the gelatin nanoparticles (GNPs) to develop hydrophilic phototherapeutic nanoagents (PTNAs, A4por-GNPs). Notably, the synthesis of such porphyrin-doped GNPs avoids the use of any toxic chemicals or solvents. The nanoprobes have also shown good fluorescence quantum yield demonstrating their applicability in bioimaging. Further, the mechanistic aspects of the anticancer and antimicrobial efficacy of the developed A4por-GNPs were evaluated via singlet oxygen generation studies. Overall, our results indicated porphyrin-doped biodegradable polymeric nanoparticles act as effective phototherapeutic agents against a broad range of cancer cell lines and microbes upon activation by the low-cost LED light.

Co-administration of zinc phthalocyanine and quercetin via hybrid nanoparticles for augmented photodynamic therapy.

The photodynamic anticancer activity of a photosensitizer can be further increased by co-administration of a flavonoid. However, this requires that both molecules must be effectively accumulated at the tumor site. Hence, in order to enhance the activity of zinc phthalocyanine (ZnPc, photosensitizer), it was co-encapsulated with quercetin (QC, flavonoid) in lipid polymer hybrid nanoparticles (LPNs) developed using biodegradable & biocompatible materials and prepared using a single-step nanoprecipitation technique. High stability and cellular uptake, sustained release, inherent fluorescence, of ZnPC were observed after encapsulation in the LPNs, which also showed a higher cytotoxic effect in breast carcinoma cells (MCF-7) compared to photodynamic therapy (PDT) alone. In vivo studies in tumor-bearing Sprague Dawley rats demonstrated that the LPNs were able to deliver ZnPc and QC to the tumor site with minimal systemic toxicity and increased antitumor effect. Overall, the photodynamic effect of ZnPc was synergized by QC. This strategy could be highly beneficial for cancer management in the future while nullifying the side effects of chemotherapy.

Development of a light activatable lignin nanosphere based spray coating for bioimaging and antimicrobial photodynamic therapy.

Many coating materials are commercially available to combat microbial infections. However, these coatings are difficult to synthesize, and are mostly composed of toxic chemicals. Lignin is an under-explored natural biopolymer with multifaceted potential. Lignin, with adhesive, UV resistant, and antimicrobial properties, is a suitable candidate to develop coating materials. Here we report a smart method to fabricate a sustainable nanospray coating from lignin which does not require any toxic chemicals or additives during synthesis. Initially, we have developed stable lignin nanospheres in a single step in aqueous medium, which were later utilized as a lignin nanospray (LNSR). The LNSR was characterized by dynamic light scattering, scanning electron microscopy, FTIR and other analytical techniques. This LNSR showed remarkable UV blocking, antioxidant and light-activated antimicrobial properties. Interestingly, for the first time, the LNSR demonstrated photoluminescence, making it useful for bioimaging. Moreover, singlet oxygen generation potential was observed in the LNSR, which could render it useful in phototheranostic applications (i.e. light assisted imaging and photodynamic therapy). Further, the LNSR was directly utilized to fabricate a sustainable coating. The nanospray coating exhibited maximum light-induced cell killing when applied to common microbes as detected by live-dead cell imaging. Taken together, the lignin nanospray coating developed via a direct pathway holds great promise to disinfect microbes in the presence of light.

Liposomal Delivery of Mycophenolic Acid With Quercetin for Improved Breast Cancer Therapy in SD Rats.

The present study explores the influence of mycophenolic acid (MPA) in combination therapy with quercetin (QC) (impeding MPA metabolic rate) delivered using the liposomal nanoparticles (LNPs). Mycophenolic acid liposome nanoparticles (MPA-LNPs) and quercetin liposome nanoparticles (QC-LNPs) were individually prepared and comprehensively characterized. The size of prepared MPA-LNPs and QC-LNPs were found to be 183 ± 13 and 157 ± 09.8, respectively. The in vitro studies revealed the higher cellular uptake and cytotoxicity of combined therapy (MPA-LNPs + QC-LNPs) compared to individual ones. Moreover pharmacokinetics studies in female SD-rat shown higher T 1 / 2 value (1.94 fold) of combined therapy compared to MPA. Furthermore, in vivo anticancer activity in combination of MPA-LNPs and QC-LNPs was also significantly higher related to other treatments groups. The combination therapy of liposomes revealed the new therapeutic approach for the treatment of breast cancer.

Lignin-Bimetallic Nanoconjugate Doped pH-Responsive Hydrogels for Laser-Assisted Antimicrobial Photodynamic Therapy.

Bioinspired nano-antimicrobials stand out in terms of cost effectiveness and scalability when compared to their chemically synthesized counterparts. There is limited efficacy of current antibiotics due to their interference with the immune system as well as development of antibiotic resistance. Lignin, which is a naturally abundant polyphenol-rich biopolymer, can be utilized for the fabrication of sustainable antimicrobial materials. In the present work, development of stable nanocomposite hydrogels embedded with lignin-based photodynamic nanoconjugates has been described. This could lead to complete eradication of microbial infection upon laser exposure. For designing such hydrogels, initially photosensitizer decorated lignin-metallic and lignin-bimetallic nanoconjugates were developed utilizing simple and nontoxic methods. These photodynamic nanoconjugates were then characterized and doped into a poly(acrylic acid)-based hydrogel in order to achieve efficient pH-triggered controlled release. The nanocomposite hydrogels allowed maximum transmission of light, promoting their applicability in antimicrobial photodynamic therapy. Utilization of hydrogel helped in better retention of nanoconjugates, maintaining their antimicrobial photodynamic efficacy as validated via IC50 measurement and live-dead cell imaging. The biocompatible pH-responsive photodynamic antimicrobial hydrogels developed herein could be potentially applicable in controlled drug delivery through the construction of wound dressings, as well as for developing antifungal, antibacterial, or antiviral nanocoatings.

Development of agri-biomass based lignin derived zinc oxide nanocomposites as promising UV protectant-cum-antimicrobial agents.

Agri-biomass derived lignin is one of the most abundant natural nontoxic organic polymers. However, a major portion of lignin is underutilized, which is being left in the fields or thrown into rivers, causing waste accumulation. Utilization of the low-cost biomass-derived lignin serves a dual purpose by reducing agri-waste and by converting it into value-added materials. Here we describe the valorization of agri-biomass based lignin via its direct utilization in the green and one-step synthesis of zinc oxide nanocomposites. Lignin offered an easy and sustainable synthesis of nanocomposites in a water-ethanol mixture without the need to use any toxic material. The lignin derived nanomaterials showed excellent potential as antioxidant, UV-blocking and antimicrobial agents due to the synergistic effect of lignin and zinc oxide. Further, these nanocomposites were incorporated as an additive into a commonly used body cream to impart UV-blocking and antimicrobial properties. This one-step, cost-effective and green synthesis technique of lignin derived zinc oxide nanocomposites not only contributes to agro-waste reduction, but at the same time helps in the production of value-added materials.

Mycophenolate co-administration with quercetin via lipid-polymer hybrid nanoparticles for enhanced breast cancer management.

Mycophenolic acid (MPA) has promising anticancer properties; however, it has limited clinical applications in vivo due to hydrophobic nature, high first-pass metabolism, lack of targeting, etc. These associated problems could be addressed by developing a suitable delivery vehicle, inhibiting the first-pass metabolism and additive/synergistic pharmacodynamic effect. Thus, MPA loaded highly stable lipid polymer hybrid nanoparticles (LPNs) were developed and investigated with the combination of quercetin (QC), a CYP 450 inhibitor cum anticancer. LPNs of MPA and QC (size; 136 ±â€¯12 and 176 ±â€¯35 nm, respectively) demonstrated higher cellular uptake and cytotoxicity of combination therapy (MPA-LPN + QC-LPN) compared to individual congeners in MCF-7 cells. In vivo pharmacokinetics demonstrated 2.17 fold higher T1/2 value and significantly higher pharmacodynamic activity in case of combination therapy compared to free MPA. In nutshell, the combinatory therapeutic regimen of MPA and QC could be a promising approach in improved breast cancer management.

Urokinase alteration and its correlation with disease severity and oxidative/nitrosative stress in buffalo calves with obstructive urolithiasis.

The present study was aimed to understand the development of bovine urolithiasis through measuring oxidative/nitrosative, cortisol and urokinase status and their relationship with disease severity. The cases of buffalo calves with obstructive urolithiasis were selected based on clinical signs, ultrasonography and laboratory examination of blood and urine (creatinine, urea nitrogen). Total 35 urolithiatic buffalo calves (urolithiatic controls) and 6 healthy calves (healthy controls) were used for study. Further, calves of urolithiatic control were sub-divided into two groups based on disease severity: mild (n = 10) and severe (n = 25) form. Oxidative/nitrosative stress were evaluated based on serum malondialdehyde (MDA), glutathione-S-transferase (GST), nitric oxide (NO) parameters. Serum cortisol was evaluated to measure stress hormone status. Serum and urine urokinase were measured and its relationship with disease severity and oxidative/nitrosative stress were established. Obstructive urolithiasis resulted in significant (p < .05) increase in biochemical parameters (creatinine, urea nitrogen), oxidant/antioxidant imbalance (increased MDA, and increased GST), nitrosative stress (increased nitric oxide), upregulated stress hormone (cortisol) in serum and elevated urokinase in serum and urine (p < .05) as compared to healthy controls. In non-parametric Kendall rank correlation (p < .01), a positive correlation was established between urokinase level and disease severity (urolithiasis). It is concluded that in bovine obstructive urolithiasis, increased oxidative/nitrosative stress, cortisol and urokinase play a significant role. The urokinase can help to understand pathophysiology of bovine urolithiasis because of having positive correlation with disease severity (urolithiasis) and stress markers.

Paclitaxel-encapsulated core-shell nanoparticle of cetyl alcohol for active targeted delivery through oral route.

Aim: Paclitaxel (PTX) has no clinically available oral formulations. Cetyl alcohol is metabolized by alcohol dehydrogenase and aldehyde dehydrogenase that are overexpressed in cancer cells. So, PTX-encapsulated core-shell nanoparticle of cetyl alcohol (PaxSLN) could target the cancer cells through oral route. Materials & methods: PaxSLN was synthesized using microemulsion template. Efficiency of PaxSLN was evaluated by ALDEFLUOR™, multicellular tumor spheroid formation inhibition assays and CT26 colorectal carcinoma animal model. Pharmacokinetics and biodistribution studies were done in Sprague Dawley rats. Results: PTX was encapsulated at the core of approximately 78 nm PaxSLN. PaxSLN targeted aldehyde dehydrogenase overexpressing cells. Its oral bioavailability was approximately 95% and chemotherapeutic efficacy was better than Taxol® and nab-PTX. Conclusion: A novel oral nanoformulation of PTX was developed.

Facile development of biodegradable polymer-based nanotheranostics: Hydrophobic photosensitizers delivery, fluorescence imaging and photodynamic therapy.

Photodynamic therapy (PDT) is reported to be a promising technique to eradicate various cancers. As most of the photosensitizers (PSs) are hydrophobic in nature, thus, the effective delivery of PSs at the targeted site is the main hurdle associated with PDT. Zinc phthalocyanine and Zinc naphthalocyanine are reported as good PSs, however, highly hydrophobic characteristics restrict their use for clinical applications. To circumvent this limitation here we developed the advanced polymer-based nano-delivery system having polyethylene glycol (PEG) coated polymeric core with ~90% PS encapsulation. The PEG coating was responsible for the stabilization of probe in the physiological environment and storage conditions. The developed theranostic probes showed efficient in vitro fluorescence and singlet oxygen quantum yields upon irradiation with 620-750 nm (30 mW/cm2) light. The clathrin-mediated endocytosis (CME) based mechanism of cellular internalization was evaluated. The fluorescence of treated MCF-7 cells showed the ability of the probes as imaging agents. Moreover, up to 65% cell inhibition showed their cytotoxic efficiency. Further, comparatively higher tumor-accumulation of PSs without significant hepato/nephro-toxicity shown in vivo experimentation using breast tumor-bearing female Sprague Dawley (SD) rats suggested the featured passive targeting ability of preparations and clinically safe to be used. The study explored the exceptional delivery system for hydrophobic PSs with commendable theranostic applications.

Self-Assembled Gold Nanoparticle-Lipid Nanocomposites for On-Demand Delivery, Tumor Accumulation, and Combined Photothermal-Photodynamic Therapy.

In this study, a distinct photoamenable nanoparticle-based drug delivery system was developed for highly efficient targeted on-demand delivery, fluorescence imaging, and therapy by incorporating zinc phthalocyanine (ZnPc) and gold nanoparticles (AuNPs) into liposomes. The hyperthermia, produced by AuNPs under LED light irradiation, enhanced the liquidity of liposomal membrane and promoted the instantaneous release of ZnPc from the carriers realizing the concept of on-demand release. In addition, the local hyperthermia also resulted in thermal damage of cancer cells along with photodynamic effect and achieved a synergetic effect of photodynamic and photothermal therapy. The developed probes showed a high breast cancer carcinoma cells (MCF-7 cell line) inhibition up to 86.7% under red light irradiation. Further, in vivo experiments suggested the high tumor accumulation as well as the antitumor effect in breast tumor-bearing female Sprague-Dawley (SD) rats. The outcomes demonstrate the capability of these probes as a novel drug delivery system to codeliver therapeutic agents with photothermal agents and will have an enormous potential for future diagnosis and therapy.

Porphyrin Functionalized Gelatin Nanoparticle-Based Biodegradable Phototheranostics: Potential Tools for Antimicrobial Photodynamic Therapy.

Photomedicine-based antimicrobial therapy has emerged as an alternative treatment for antibiotic-resistant microbial infections. Although various photosensitizers (PSs) have been reported as efficient antimicrobial agents, their efficient delivery to the specific target area requires further investigation. In the current study, development of a biodegradable phototheranostic nanoagent (PTNA) by incorporation of a PS (trans-AB-porphyrin) and gelatin nanomatrix is described. The antimicrobial efficacy of the PTNA against Gram-positive bacteria, Gram-negative bacteria, and yeast strains, along with other properties including hydrophilicity, biocompatibility, and targeting ability, is evaluated. Unlike the commonly used membrane permeabilizing chemicals that are toxic, the delivery vehicle gelatin used in this study is biocompatible and biodegradable. Here, the method offers a sustainable synthesis of gelatin-based stable formulation of nanotheranostic agents with high loading (>85%). The study revealed that the reactive oxygen species (ROS), generated in situ by the PTNAs, are primarily responsible for microbial cell death. The developed PTNAs described herein featured "nano size (<200 nm), have high fluorescence and singlet oxygen quantum yields, retain photophysical properties of PS after incorporation into the gelatin matrix, could be activated by a cost-effective light irradiation, and have efficient antimicrobial photodynamic activity." This antimicrobial photodynamic therapy using the newly synthesized phototheranostic nanoagent has manifested its competence, therapeutic modality of general acceptance, and wide-spectrum antimicrobial action.

Engineering Lignin Stabilized Bimetallic Nanocomplexes: Structure, Mechanistic Elucidation, Antioxidant, and Antimicrobial Potential.

Lignin, being a natural antioxidant and antimicrobial underutilized biopolymer derived mainly from agro-waste, is a material of great interest. In this study, lignin was chosen as a matrix to synthesize silver-gold bimetallic and monometallic nanocomplexes to explore the synergistic antioxidant and antimicrobial properties of the lignin stabilized nanoagents. The synthesis of the nanocomplexes was carried out using a one pot method, utilizing lignin as the sole source for reducing, capping, and stabilizing the nanoagents. Further, characterization studies were performed to determine the exact structure of the nanocomplexes. The developed nanocomplexes were found to possess substantial phenolic and flavonoid contents, which contributed to their high antioxidant activity. Further, the antioxidant and antimicrobial activity of the lignin-bimetallic and monometallic nanocomplexes was evaluated and compared with pristine lignin. Moreover, the mechanism behind the antimicrobial activity of the nanocomplexes was elucidated through various methods, namely, reactive oxygen generation, nucleic acid leakage, and DNA cleavage studies. The obtained results were greatly supported by scanning electron microscopy, transmission electron microscopy, and live-dead cell imaging techniques. This study is a contribution in converting waste to value added functional nanomaterials for potential antioxidant and antimicrobial applications.

Development of Gelatin Nanoparticle-Based Biodegradable Phototheranostic Agents: Advanced System to Treat Infectious Diseases.

Rose bengal (RB)-conjugated and -entrapped gelatin nanoparticle (GNP)-based biodegradable nanophototheranostic (Bd-NPT) agents have been developed for the efficient antimicrobial photodynamic therapy. The study reveals that the use of gelatin nanoparticles could bypass the chemicals such as potassium iodide, EDTA, calcium chloride and polymyxin nonapeptide for the penetration of drug into the cell membrane to achieve antimicrobial activity. We demonstrated that the singlet oxygen generated by the biodegradable gelatin nanoparticles (BdGNPs) could damage the microbial cell membrane and the cell dies. The key features of the successive development of this work include the environmentally benign amidation of RB with GNPs, which was so far unexplored, and the entrapment of RB into the gelatin nanoparticles (GNP). The RB-GNP exhibited potent and broad-spectrum antimicrobial activity and could be useful in treating multi-drug-resistant microbial infections.

Esterase-Mediated Highly Fluorescent Gold Nanoclusters and Their Use in Ultrasensitive Detection of Mercury: Synthetic and Mechanistic Aspects.

The fast, accurate, and ultrasensitive detection of toxic mercury in real water samples is still challenging without the use of expensive sophisticated instruments. Herein, highly fluorescent gold nanoclusters (AuNCs) were synthesized using a newer protein templet, esterase (EST). The EST-AuNCs consisted of ∼25 Au atoms in the nanocluster having ∼2 nm size. EST-AuNCs were found to be highly stable in aqueous buffer with a wide range of pH (pH 4-12) and were also stable in powdered form. The fluorescence quantum yield of EST-AuNCs in deionized water was 6.2% which had increased to 7.8% upon the addition of 1 M NaCl (an increase of 23%). The EST-AuNCs selectively sense the toxic Hg2+ ions with higher sensitivity (limit of detection; 0.88 nM) with the linear range 1-30 nM. The test strips for rapid sensing of Hg2+ in real water samples were developed on the polymeric surface. The validation of sensing ability of EST-AuNCs suggested 94-98% recovery with linearity. Moreover, because of the widely reported applications of EST, the developed EST-AuNCs could also be used for another sensing, catalytic, and biomedical applications.