Biogenic Synthesis of Fluorescent Carbon Dots at Ambient Temperature Using Azadirachta indica (Neem) gum.

Synthesis of fluorescent Carbon Dots (CDs) from various carbonaceous materials apparently has acquired lots of interest amongst researchers as the corollary of the properties of CDs; which are subsequently getting unveiled. In this study we report the use of Azadirachta indica (Neem) Gum as a novel natural pre-cursor for synthesis of CDs at room temperature. Water soluble CDs of around 5-8 nm were obtained after treatment of the gum with ethanol and NaOH. These CDs exhibited green fluorescence in UV-light (λ = 365 nm). These CDs were found to be stable, having many bio-linkers attached on their surface, making it suitable for drug attachment and hence can serve as potential candidates for applications like drug delivery vehicles as well as for biosensors.

A green route towards highly photoluminescent and cytocompatible carbon dot synthesis and its separation using sucrose density gradient centrifugation.

An efficient, fast and green method for synthesis of Carbon dots (C-dots) using natural precursor Citrus limone under ultrasonic condition is demonstrated. Such as-synthesized C-dots were further purified using Sucrose density gradient centrifugation method (SDGC) which resulted in the separation of water-soluble, photo luminescent, monodispersed, highly photostable and chemically stable C-dot fractions (F1 and F2). They possess very small size (5-20 nm) as evidenced by High angle annular dark field-Scanning Transmission electron microscopy (HAADF-STEM) and very strong luminescence as shown by fluorescence spectroscopic studies. Cytocompatibility and bio imaging properties of both the fractions (F1 and F2) were then studied on Hep-2 cells. Quantum yield of F1 and F2 fraction was found to be 12.1 and 15 %, respectively.

Gold nanorods mediated controlled release of doxorubicin: nano-needles for efficient drug delivery.

Use of cysteamine hydrochloride (Cys-HCl) protected gold nanorods (GNRs) as efficient carrier of widely used anti-cancer drug doxorubicin using folic acid as navigational molecule is presented in this work. GNRs were found to have excellent drug loading capacity of >97 %. A detailed comprehension of in vitro drug release profile under ideal physiological condition was found to obey 1st order kinetics at pH 6.8, 5.3 and 7.2, an ideal milieu for drug delivery to solid tumours.

Progress on Applying Carbon Dots for Inhibition of RNA Virus Infection.

Viral infection is a globally leading health issue. Annually, new lethal RNA viruses unexpectedly emerged and mutated threatening health and safety. Meanwhile, it is urgent to explore novel antiviral agents, which, however, takes years to be clinically available. Nonetheless, the development of carbon dots (CDs) in the past 20 years has exhibited their vast application potentials and revealed their promising capacity as future antiviral agents considering their versatile properties and significant antiviral responses. Thus, CDs have been widely investigated as an alternative of traditional chemotherapy for inhibiting viral infection and replication in vitro. Meanwhile, attempts to apply CDs to in vivo systems are in high demand. In this review, recent developments of CDs-based antiviral therapies are systematically summarized. Furthermore, the role of CDs in photodynamic inactivation to kill viruses or bacteria is briefly discussed.

Milk-derived multi-fluorescent graphene quantum dot-based cancer theranostic system.

An economical green-chemistry approach was used for the synthesis of aqueous soluble graphene quantum dots (GQDs) from cow milk for simultaneous imaging and drug delivery in cancer. The GQDs synthesized using one-pot microwave-assisted heating were multi-fluorescent, spherical in shape having a lateral size of ca. 5nm. The role of processing parameters such as heating time and ionic strength showed a profound effect on photoluminescence properties of GQDs. The GQDs were N-doped and oxygen-rich as confirmed by X-ray photoelectron spectroscopy (XPS) analysis. Cysteamine hydrochloride (Cys) was used to attach an anti-cancer drug berberine hydrochloride (BHC) on GQDs forming GQDs@Cys-BHC complex with c.a. 88% drug loading efficiency. In vitro drug release was studied at the acidic-basic environment and drug kinetics was studied using pharmacokinetic statistical models. The GQDs were biocompatible on L929 cells whereas theranostic GQDs@Cys-BHC complex showed a potent cytotoxic effect on different cancerous cell line models: cervical cancer cell lines such as HeLa cells and breast cancer cells such as MDA-MB-231 confirmed by Trypan blue and MTT-based cytotoxic assays. Furthermore, multi-excitation based cellular bioimaging was demonstrated using confocal laser scanning microscopy (CLSM) and fluorescence microscopy using GQDs as well as GQDs@Cys-BHC complex. Thus, drug delivery (therapeutic) and bioimaging (diagnostic) properties of GQDs@Cys-BHC complex are thought to have a potential in vitro theranostic application in cancer therapy.

Camphor-mediated synthesis of carbon nanoparticles, graphitic shell encapsulated carbon nanocubes and carbon dots for bioimaging.

A green method for an efficient synthesis of water-soluble carbon nanoparticles (CNPs), graphitic shell encapsulated carbon nanocubes (CNCs), Carbon dots (CDs) using Camphor (Cinnamomum camphora) is demonstrated. Here, we describe a competent molecular fusion and fission route for step-wise synthesis of CDs. Camphor on acidification and carbonization forms CNPs, which on alkaline hydrolysis form CNCs that are encapsulated by thick graphitic layers and on further reduction by sodium borohydride yielded CDs. Though excitation wavelength dependent photoluminescence is observed in all the three carbon nanostructures, CDs possess enhanced photoluminescent properties due to more defective carbonaceous structures. The surface hydroxyl and carboxyl functional groups make them water soluble in nature. They possess excellent photostability, higher quantum yield, increased absorption, decreased cytotoxicity and hence can be utilized as a proficient bio imaging agent.

Antimicrobial activity of crude extracts from plant parts and corresponding calli of Bixa orellana L.

Ethanol extracts from the different parts of B. orellana showed differential antimicrobial activity. It was found that the extracts of in vitro leaves showed maximum activity against Bacillus pumilus followed by the extracts from the roots and hypocotyls. The callus derived from different explants too showed antimicrobial activity. The leaf callus showed maximum activity. The zone of inhibition for the diluted extracts of in vitro hypocotyls and roots and their corresponding calli showed minimum zone of inhibition at concentration 24 mg/ml, whereas the diluted extract of in vitro leaves and leaf derived callus showed minimum zone of inhibition at 16 mg/ml.

Swarming carbon dots for folic acid mediated delivery of doxorubicin and biological imaging.

Carbon dots (C-dots) are one of the most highlighted carbon-based materials for biological applications such as delivery of therapeutic payloads for cancer treatment mainly due to their biocompatibility and unique optical properties. In this work, we have explored the drug carrying capacity of highly fluorescent sorbitol-derived C-dots for targeted delivery of doxorubicin (DOX). We have used folic acid (FA) as a navigational molecule due to its high expression in most cancer cells. Before attachment of the DOX, the surfaces of the C-dots were protected with bovine serum albumin (BSA) to make them more biocompatible and able to hold a high amount of drugs. The release profile of DOX was studied using standard statistical models and confirmed to be first order at pH 7.2. Cellular imaging was performed using epifluorescence microscopy, which showed bright green coloured fluorescence due to internalization of C-dots specifically targeted with FA in HeLa cells.

Biogenic gold nano-triangles: cargos for anticancer drug delivery.

We present synthesis of biogenic gold nano triangles (GNTs) using Azadirachta indica leaf extract at inherent pH (5.89) and its application in efficient drug delivery of doxorubicin (DOX) (anticancer drug). The main idea was to take advantage of large surface area of GNTs which has 3 dimensions and use the plant peptides coated on these triangles as natural linkers for the attachment of DOX. Sucrose density gradient centrifugation (SDGC) and dialysis methods were used for separation of the GNT from mixture of GNPs. Flocculation parameter (FP) was used to check stability of GNT which was found to be exceptionally high (0-0.75) due to the biological capping agents. DOX attachment to GNT was verified using Fourier transformed infra-red (FTIR) spectroscopy. The complex thus formed was found to be less toxic to normal cells (MDCK cells) and significantly toxic for the cancerous cells (HeLa cells). Drug loading efficiency was found to be 99.81% and DOX release followed first order release kinetics. Percentage drug release was found to be more than 4.5% in both acidic (5.8) as well as physiological pH (7.2) which is suitable for tumor targeting.

Antibiotic conjugated fluorescent carbon dots as a theranostic agent for controlled drug release, bioimaging, and enhanced antimicrobial activity.

A novel report on microwave assisted synthesis of bright carbon dots (C-dots) using gum arabic (GA) and its use as molecular vehicle to ferry ciprofloxacin hydrochloride, a broad spectrum antibiotic, is reported in the present work. Density gradient centrifugation (DGC) was used to separate different types of C-dots. After careful analysis of the fractions obtained after centrifugation, ciprofloxacin was attached to synthesize ciprofloxacin conjugated with C-dots (Cipro @ C-dots conjugate). Release of ciprofloxacin was found to be extremely regulated under physiological conditions. Cipro @ C-dots were found to be biocompatible on Vero cells as compared to free ciprofloxacin (1.2 mM) even at very high concentrations. Bare C-dots ( ∼ 13 mg mL(-1)) were used for microbial imaging of the simplest eukaryotic model-Saccharomyces cerevisiae (yeast). Bright green fluorescent was obtained when live imaging was performed to view yeast cells under fluorescent microscope suggesting C-dots incorporation inside the cells. Cipro @ C-dots conjugate also showed enhanced antimicrobial activity against both model gram positive and gram negative microorganisms. Thus, the Cipro @ C-dots conjugate paves not only a way for bioimaging but also an efficient new nanocarrier for controlled drug release with high antimicrobial activity, thereby serving potential tool for theranostics.

A comparative study of economical separation and aggregation properties of biologically capped and thiol functionalized gold nanoparticles: selecting the eco-friendly trojan horses for biological applications.

We are presenting facile bio-fabrication of extremely stable gold nanoparticles (GNPs) using medicinal plant Azadirachta indica (commonly called Neem) and its comparison with most commonly used glutathione (GSH) protected GNPs in terms of stability under physiological conditions, seperation using density gradient centrifugation and aggregation properties in the solution. There was dual peak at 536 and 662 nm indicating the presence of non-spherical GNPs including triangles, rods and hexagons in case of A. indica mediated GNPs unlike citrate stabilized GNPs which exhibited single sharp peak. Spherical GNPs were separated from the consortium of uniquely shaped nanoparticles bio-fabricated using A. indica leaf extract using sucrose density gradient centrifugation (SDGC).To comprehend the anti-agglomeration potentials of A. indica leaf mediated GNPs and GSH-GNPs under physiological conditions, flocculation parameters (FP) were calculated and found to be least for A. indica leaf mediated GNPs, indicating their exceptional stability.

Understanding the stability of silver nanoparticles bio-fabricated using Acacia arabica (Babool gum) and its hostile effect on microorganisms.

We report green synthesis of stable silver nanoparticles (SNPs) from Acacia arabica gum and its anti-bacterial activity against gram-positive and gram-negative bacteria. UV-Vis spectral analysis of synthesized SNPs showed maximum peak at 462 nm initially and 435 nm after 24 h. Using Transmission Electron microscopy (TEM), the average size of synthesised SNPs was found to be ~35 nm. X-ray diffraction (XRD) and Selective area electron diffraction (SAED) pattern confirmed the crystalline nature of SNPs. Percentage conversion of Ag(+) ions into Ag° was calculated using ICP-AES and was found to be 94%. By calculating flocculation parameter, we could see that these SNPs are extremely stable under the influence of very high NaCl concentration up to 4.16 M. These stable SNPs can be used in various industrial and medical applications.

Folic acid mediated synaphic delivery of doxorubicin using biogenic gold nanoparticles anchored to biological linkers.

Azadirachta indica as a biological sink for fabrication of gold nanoparticles (GNPs) and its applications in efficient delivery of doxorubicin (DOX) are presented here. Sucrose density gradient centrifugation was used to isolate the spherical GNPs of <50 nm from the mixture (containing both spherical and non-spherical) of nanoparticles synthesized using leaves of A. indica at inherent pH (6.14). The stability of GNPs due to the biological capping agents was scrutinised by measuring the flocculation parameter which was found to be in the range of 0-0.65. On the surface of these capped GNPs, doxorubicin was attached along with activated folic acid (FA) as navigational molecules for targeted drug delivery. Attachments were verified using FTIR which confirmed the formation of non-covalent interactions. The GNPs-FA-DOX complex was found be non-toxic for normal cells and considerably toxic for HeLa cells. The drug loading capacity of the GNPs was found to 93%. Doxorubicin release kinetics using GNPs followed 1st order at pH 5.3 which is ideal for solid tumor targeting.

Carbon dots functionalized gold nanorod mediated delivery of doxorubicin: tri-functional nano-worms for drug delivery, photothermal therapy and bioimaging.

Carbon dots (C-dots) are novel nanomaterials for biological applications owing to their inherent surface decoration by a variety of functional groups, excellent fluorescent properties and biocompatibility under physiological conditions. Gold nanorods (GNRs) are one of the most celebrated nanomaterials for photothermal therapy as well as delivery of therapeutic payloads because of their typical size and shape related features. We have synthesized a unique blend of C-dots and GNRs (C-dots@GNRs) for the controlled release of doxorubicin (DOX) under ideal physiological conditions. Highly fluorescent C-dots were synthesized using microwave assisted heating of gum arabic (GA) and subsequently purified using Sucrose Density Gradient Centrifugation (SDGC). In a modified seed mediated protocol, purified C-dots were added into the growth solution, to make a C-dots@GNR complex. This complex was used for anchoring DOX via covalent and non-covalent pH sensitive chemical bonds. Under physiological conditions, the drug loading capacity of C-dots@GNRs was calculated to be ∼94%. Another beneficial attribute of the complex was found to be synergistic potential in high drug loading and rapid burst of drug release under the influence of near infrared (NIR) radiation (808 nm), thus proving a highly biocompatible thermo-chemotherapy for solid tumors.

Biogenic gold nanoparticles as fotillas to fire berberine hydrochloride using folic acid as molecular road map.

Use of biologically modified gold nanoparticles (GNPs) as molecular vehicle to ferry potential anti-cancer drug berberine hydrochloride (BHC) using folic acid (FA) as targeting molecule is reported in this work. A tropical fruit peel, Trapa bispinosa is used to fabricate highly monodispersed GNPs, passivated with essential functional groups which were used as linkers to attach FA and BHC via amide linkage. Flocculation Parameter (FP) of biologically synthesized GNPs was calculated under different salt concentrations which were found to be very ideal under a physiological condition. Various statistical models were used to find drug release profile out of which Higuchi was found to be the most ideal. GNP-FA-BHC complexes were found to be active against folic acid expressing HeLa cells.

Green synthesis of biocompatible carbon dots using aqueous extract of Trapa bispinosa peel.

We are reporting highly economical plant based method for the production of luminescent water soluble carbon dots (C-dot) using Indian water plant Trapa bispinosa peel extract without adding any external oxidizing agent at 90 °C. C-dots ranging from 5 to 10nm were found in the solution with a prominent green fluorescence under UV-light (λex=365 nm). UV-vis spectra recorded at different time intervals (30-120 min) displayed signature absorption of C-dots between 400 and 600 nm. Fluorescence spectra of the dispersion after 120 min of synthesis exhibited characteristic emission peaks of C-dots when excited at 350, 400, 450 and 500 nm. C-dots were further analyzed using X-ray diffraction (XRD), Raman Spectroscopy and Thermo-Gravimetric Analysis (TGA). Structure of the C-dots was found to be turbostratic when studied using XRD. C-dots synthesized by our method were found to be exceptionally biocompatible against MDCK cells.

Photocatalysis-assisted water filtration: using TiO2-coated vertically aligned multi-walled carbon nanotube array for removal of Escherichia coli O157:H7.

A porous ceramic was coated with vertically aligned multi-walled carbon nanotubes (MWCNTs) by spray pyrolysis. Titanium dioxide (TiO2) nanoparticles were then coated onto this densely aligned MWCNT. The presence of TiO2/MWCNT interfacial arrays was confirmed by X-ray diffraction (XRD), scanning electron microscope-energy dispersive analysis of X-ray (SEM-EDAX) and transmission electron microscope (TEM). This is a novel report in which water loaded with a most dreadful enterohemorrhagic pathogenic strain of Escherichia coli O157:H7 was filtered through TiO2/MWCNT coated porous ceramic filter and then analysed. Bacterial removal performance was found to be significantly lower in control i.e. plain porous ceramic (P<0.05) as compared to TiO2/MWCNT coated ceramic. The photocatalytic killing rate constant for TiO2-ceramic and MWCNT/TiO2-ceramic under fluorescent light was found be 1.45×10(-2) min(-1) and 2.23×10(-2) min(-1) respectively. Further, when I-V characteristics were performed for TiO2/MWCNT composite, it was corroborated that the current under light irradiation is comparatively higher than that in dark, thus proving it to be photocatalytically efficient system. The enhanced photocatalysis may be a contribution of increased surface area and charge transfer rate as a consequence of aligned MWCNT network.