Mukeshchand Thakur

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.

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.

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.

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.

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.

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.

Synthesis of highly fluorescent hydrophobic carbon dots by hot injection method using Paraplast as precursor.

We have reported synthesis of bright blue colored hydrophobic carbon dots (hC-dots) using highly pure blend of polymers called Paraplast. We developed a hot injection method for making nearly monodispersed hC-dots with a diameter in a range: 5-30nm as confirmed by high resolution transmission electron microscopy (HRTEM). The involvement of various functional groups was confirmed by Fourier transform infra-red (FTIR) spectroscopy. These hC-dots were incubated with breast cancer stem cells in order to check the entry as well as biological imaging. The cells were analyzed using epifluorescent microscopy. hC-dots showed concentration dependent cytotoxicity (LD50: 50mg/ml) and could be used for bioimaging even at lower concentration (0.5mg/ml). hC-dots were found to be versatile agents for peeping inside the cells which could also be used for delivery of water insoluble chemotherapeutic agents to variety of solid tumors.

Synthesis of mesoporous silica oxide/C-dot complex (meso-SiO2/C-dots) using pyrolysed rice husk and its application in bioimaging

Due to the abundance of silica and carbon in rice (Oryza sativa) husk (RH), we exploited it for the synthesis of a mesoporous silica oxide micro-particles (meso-SiO2)/C-dot complex for biological imaging using a novel hot injection method commonly used for semiconductor quantum dots. Carbon dots (C-dots) with a high degree of green fluorescence were observed under UV-light they were found to be embedded to a significant extent in meso-SiO2 as confirmed by transmission electron microscopy (TEM) and energy dispersive spectroscopy (EDS). The mesoporous nature of the complex was confirmed using N2 adsorption–desorption measurements. Surface functionalization was studied using Fourier transform infrared spectroscopy (FTIR). The synthesized meso-SiO2/C-dots complex was used for labeling yeast cells since the fungi closely represents eukaryotic organisms. Furthermore, the meso-SiO2/C-dot complex was found to be highly bio-compatible for Vero cells. This study might help in the further utilization of the complex for the theranostic application of simultaneous cellular imaging and drug delivery.

Cysteamine hydrochloride protected carbon dots as a vehicle for the efficient release of the anti-schizophrenic drug haloperidol

The use of phenylalanine derived non-toxic carbon dots (C-dots) as a vehicle for the delivery of widely used anti-psychotic drug haloperidol (HaLO) is described in the present research work. The C-dots were found to have remarkable optical properties and to exhibit bright green fluorescence under UV light (λex = 365 nm). The UV-Vis spectrum of the C-dots exhibits peaks at 232 and 276 nm confirming their synthesis in solution. The size of the C-dots was found to be in the range of 5–10 nm, as confirmed by Field Emission Scanning Electron Microscopy (FE-SEM). Cysteamine hydrochloride (CysHCl) was used as a non-toxic linker to functionalize the purified C-dots before grafting HaLO on the surface to facilitate the controlled release under physiological conditions. A constant release of HaLO was achieved for more than 40 h, which followed the Hixson–Crowell model under standardized conditions. The C-dot–CysHCl–HaLO conjugate was found to have a much higher compatibility with MDCK cells at pH 7.2 in comparison to bare HaLO.

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.