Sudeshna Chandra

Oxide and hybrid nanostructures for therapeutic applications

The research on biomedical applications of nanoparticles has seen an upsurge in recent years due to their unique capabilities in treatment of ailments. Though there are ample reviews on the advances of nanoparticles right from their fabrication to applications, comparatively fewer reviews are available for the nanostructured materials particularly on oxides and hybrids. These materials possess unique physicochemical properties with an ability to get functionalized at molecular and cellular level for biochemical interactions. Keeping the enormosity of the nanostructures in mind, we intend to cover only the recent and most noteworthy developments in this area. We, particularly emphasize on iron oxide and its derivatives, zinc oxides, layered double hydroxides, silica and binary/ternary metal oxides and their applications in the area of therapeutics. This review also focuses on the designing of biodegradable and biocompatible nanocarriers and critical issues related to their therapeutic applications. Several representative examples discuss targeting strategies and stimuli responsive nanocarriers and their therapeutics.

Dendritic magnetite nanocarriers for drug delivery applications

A novel arginine-based dendritic block is grown on the surface of APTS-coated Fe3O4 nanoparticles by conventional growth approach of Michael addition/amidation reactions. The thus-obtained dendritic magnetite nanocarriers (DMNCs) were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), atomic force microscopy (AFM), vibrating sample magnetometry(VSM), dynamic light scattering (DLS) and thermogravimetric (TGA) analysis. The functionalization of MNPs with the dendritic block was evident from FTIR and TGA analyses. The nanocarriers had an average size of 10 nm and exhibited superparamagnetism with high magnetization values at room temperature. The aqueous colloidal suspension of DMNCs (10 mg ml−1 of Fe) showed a temperature rise up to 43 °C in 5 min and yielded a moderate specific absorption rate (SAR) value of 30 W g−1 of magnetite under the influence of AC magnetic field of 10 kA m−1 and 425 kHz frequency. Biocompatibility of the developed nanocarriers was evaluated in vitro by assessing their cytotoxicity on human cervical cancer cells (HeLA cells) using a sulforhodamine B (SRB) assay. Encapsulation and release of the anticancer drug doxorubicin (DOX) was investigated. The change in surface charge, as evident from zeta potential analyzer and quenching of fluorescence intensity, strongly suggests the interaction of DOX with the DMNCs. The nanocarriers showed good capacity to encapsulate DOX, with loading as high as 65% (w/w) and a pH-responsive sustained release of 54% at pH 5.0. Also, the release of DOX from the nanocarriers increased up to 80% on application of an AC magnetic field.

SnO2 Quantum Dots-Reduced Graphene Oxide Composite for Enzyme-Free Ultrasensitive Electrochemical Detection of Urea

Most of the urea sensors are biosensors and utilize urease, which limit their use in harsh environments. Recently, because of their exceptional ability to endorse faster electron transfer, carbonaceous material composites and quantum dots are being used for fabrication of a sensitive transducer surface for urea biosensors. We demonstrate an enzyme free ultrasensitive urea sensor fabricated using a SnO2 quantum dots (QDs)/reduced graphene oxide (RGO) composite. Due to the synergistic effect of the constituents, the SnO2 QDs/RGO (SRGO) composite proved to be an excellent probe for electrochemical sensing. The morphology and structure of the composite was characterized by various techniques, and it was observed that SnO2 QDs are decorated on RGO layers. Electrochemical studies were performed to evaluate the characteristics of the sensor toward detection of urea. Amperometry studies show that the SRGO/GCE electrode is sensitive to urea in the concentration range of 1.6 × 10(-14)-3.9 × 10(-12) M, with a detection limit of as low as 11.7 fM. However, this is an indirect measurement for urea wherein the analytical signal is recorded as a decrease in the amperommetric and/or voltammetric current from the solution redox species ferrocyanide. The porous structure of the SRGO matrix offers a very low transport barrier and thus promotes rapid diffusion of the ionic species from the solution to the electrode, leading to a rapid response time (∼5 s) and ultrahigh sensitivity (1.38 μA/fM). Good analytical performance in the presence of interfering agents, low cost, and easy synthesis methodology suggest that SRGO can be quite promising as an electroactive material for effective urea sensing.

Poly(ethylene glycol)-modified PAMAM-Fe3O4-doxorubicin triads with the potential for improved therapeutic efficacy: generation-dependent increased drug loading and retention at neutral pH and increased release at acidic pH.

Polyamidoamine (PAMAM) dendrimer-coated magnetic nanoparticles are a promising drug-delivery system that can enhance the therapeutic effects of chemotherapy drugs, such as doxorubicin (DOX), with minimized side effects. This work explores the optimization of the potential therapeutic efficiency of PAMAM-Fe3O4-DOX triads. Different generations (G3, G5, and G6) of PAMAMs were synthesized and modified with poly(ethylene glycol) (PEG) and then used to encapsulate glutamic acid-modified Fe3O4 nanoparticles. The Fe3O4-dendrimer carriers (Fe3O4-DGx where x = the generation 3, 5, or 6 of dendrimers) were electrostatically conjugated with drug DOX. The loading and releasing efficiencies of DOX increased with the PAMAM generation from 3 to 6. The loading efficiencies of DOX molecules were 87, 93, and 96% for generations 3, 5, and 6, respectively. At pH 5, the DOX release efficiencies within 24 h were approximately 60, 68, and 80% for generations 3, 5, and 6, respectively. At pH 7.4, the DOX releasing efficiency was as low as ∼ 15%. Compared to the negative control, the PAMAM-Fe3O4-DOX triads showed only mild toxicity against human cervical adenocarcinoma cell line HeLa at pH 7.4, which indicated that DOX can be fairly benignly carried and sparingly released until PAMAM-Fe3O4-DOX is taken up into the cell.

Dendrimer facilitated synthesis of multifunctional lanthanide based hybrid nanomaterials for biological applications

A poly(amido amine) (PAMAM) dendrimer has been successfully used for the first time as a linking agent for the synthesis of a luminescent lanthanide based multifunctional nanohybrid (YPO4:Tb3+@Fe3O4). Characterization of the materials was done by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), vibrating sample magnetometer (VSM), and thermogravimetric analysis (TGA). The HRTEM images showed spindle shaped YPO4:Tb3+@Fe3O4 in the presence of a PAMAM dendrimer which is due to the incorporation of the Fe3O4 nanoparticles in the branches of the PAMAM dendrimer when they are attached on the surfaces of the YPO4:Tb3+ nanorods. Photoluminescence studies showed the Tb–O charge transfer transition which is produced by electron delocalization from the filled 2p shell of the O2− to the partially filled 4f shell of Tb3+. The nanohybrid materials yielded a specific absorption rate (SAR) value of 39.22 W g−1 of magnetite under the influence of an AC magnetic field of 110 Oe and 425 kHz frequency. Biocompatibility of the developed hybrid nanomaterials was evaluated in vitro by assessing their cytotoxicity on human cervical cancer cells (HeLa cells) using a sulforhodamine B (SRB) assay. These YPO4:Tb3+@Fe3O4 nanohybrids have potential biomedical applications in the area of imaging and magnetic hyperthermia.

Polyaniline-iron oxide nanohybrid film as multi-functional label-free electrochemical and biomagnetic sensor for catechol.

Polyaniline-iron oxide magnetic nanohybrid was synthesized and characterized using various spectroscopic, microstructural and electrochemical techniques. The smart integration of Fe3O4 nanoparticles within the polyaniline (PANI) matrix yielded a mesoporous nanohybrid (Fe3O4@PANI) with high surface area (94 m(2) g(-1)) and average pore width of 12.8 nm. Catechol is quasi-reversibly oxidized to o-quinone and reduced at the Fe3O4@PANI modified electrodes. The amperometric current response toward catechol was evaluated using the nanohybrid and the sensitivity and detection limit were found to be 312 μA μL(-1) and 0.2 nM, respectively. The results from electrochemical impedance spectroscopy (EIS) indicated that the increased solution resistance (Rs) was due to elevated adsorption of catechol on the modified electrodes. Photoluminescence spectra showed ligand-to-metal charge transfer (LMCT) between p-π orbitals of the phenolate oxygen in catechol and the d-σ* metal orbital of Fe3O4@PANI nanohybrid. Potential dependent spectroelectrochemical behavior of Fe3O4@PANI nanohybrid toward catechol was studied using UV/vis/NIR spectroscopy. The binding activity of the biomagnetic particles to catechol through Brownian relaxation was evident from AC susceptibility measurements. The proposed sensor was used for successful recovery of catechol in tap water samples.

Mechanistic insights into the interactions of magnetic nanoparticles with bovine serum albumin in presence of surfactants.

This work reports the physicochemical parameters and the nature of association between magnetic nanoparticles and bovine serum albumin (BSA) in presence of cationic and anionic surfactants. Magnetic iron oxide nanoparticles (MNPs) are first synthesized using chemical co-precipitation method and subsequently characterized by FTIR, XRD, DLS, TEM and Zeta potential. The bare nanoparticles are then coated with BSA and their interactions studied using fluorescence spectroscopy, dynamic light scattering and circular dichroism techniques. The spectroscopic investigation sheds light into various aspects of binding and size variation during the molecular association of BSA with the MNPs in absence and presence of cationic and anionic surfactants. Isothermal titration calorimetry was used to probe the thermodynamic parameters of the systems. MNPs-BSA system was found to be more stable in presence of cationic surfactant. This study provides valuable mechanistic insights into the interactions taking place at the interface of the nanoparticles which further helps in designing a stable colloidal MNPs systems.

Fabrication of a label-free electrochemical immunosensor using a redox active ferrocenyl dendrimer

We report an IgG (=immunoglobulin) electrochemical immunosensor using a newly synthesized redox-active ferrocenyl dendrimer of generation 2 (G2Fc) as a voltammetric transducer. The ferrocenyl dendrimer N(CH2CH2C(O)NHCH2CH2NHC(O)Fe(η5-C5H4)(η5-C5H5))(CH2CH2N(CH2CH2C(O)NHCH2CH2NHC(O)Fe(η5-C5H4)(η5-C5H5))2)2 (G2Fc) was used as a functional moiety to immobilize the antibody on the surface of the electrode. A sandwich immunosensor of the type IgG/Bovine serum albumin (BSA)/anti-IgG/G2Fc/glassy carbon electrode (GCE) was fabricated. The electrochemical properties of G2Fc were thoroughly studied in aqueous and non-aqueous electrolytes with varying scan rates. The incubation time was optimized for better analytical performance of the immunosensor. It is found that the developed amperometric immunosensor is sensitive to a concentration of IgG as low as 2 ng mL−1.

Detailed toxicity evaluation of β-cyclodextrin coated iron oxide nanoparticles for biomedical applications

The application of iron oxide nanoparticles [IONPs] in biomedical research is progressively increasing, leading to the rapid development of biocompatible and surface modified IONPs. However, there is still a need of information pertaining to its cellular and acute toxicity profile. This work reports the synthesis of β-cyclodextrin coated iron oxide nanoparticles (βCD-IONPs) and their characterization using spectroscopic (FT-IR), thermal (TGA) and surface analysis (TEM, SEM, BET and Zeta potential). All the characterization techniques displayed the synthesis of well dispersed, rod shaped βCD-IONPs of 45nm. Time dependent cellular uptake of these nanoparticles was also evaluated using Prussian blue staining. Further, cytocompatibility analysis was executed in mouse fibroblast cell line (NIH 3T3) using MTT and LDH assays, respectively which did not show any cytotoxic indications of βCD-IONPs. Finally, acute toxicity analysis was carried out in female Wistar rats according to OECD guidelines 420. Rats were exposed to the highest dose (2000mg/kg) of βCD-IONPs along with control and observed for 14days. After two weeks of administration, tissues and blood were collected and subjected to histopathological and biochemical analysis (SGOT, SGPT and ALP). Animals were sacrificed and gross necropsy was carried out. It has been shown that βCD-IONPs does not have any significant toxic effect at the cellular level. Thus, this study provides new perspectives for future biomedical applications.

PAMAM dendrimers: A multifunctional nanomaterial for ECL biosensors

Polyamido amine (PAMAM) dendrimers have been shown to function as electrochemiluminescence (ECL) co-reactant and have the inherent capability of improving immobilization of molecules on surfaces due to their dendritic structure. Here, we investigated the combination of both of these properties as the basis for biosensor development. Dendrimers with 5, 8, 10 and 16 terminal amine groups, respectively, were used. These were covalently coupled to biotin as model recognition site, and tagged with Ru(bpy)32+ via adsorption. Due to their hydrophilicity, Ru-dendrimers showed significantly improved electrochemical activity in comparison to the standard tripropylamine (TPA) assisted ECL and similar luminescence yields even though 10 fold less dendrimer concentration was required in comparison to TPA. Best signals were obtained for D8 and D10 dendrimers. These Ru-dendrimers were subsequently used for the quantification of streptavidin, as its binding to the biotin-tag caused a proportional decrease in ECL signal with a dynamic range of 5nM to 1μM. These preliminary studies demonstrate that PAMAM dendrimers can function as responsive signal generators in solution-based ECL-bioassays with an assumed even higher impact when being immobilized directly on the electrode-surface.