Saumya Nigam

Nanoscale assembly of mesoporous ZnO: A potential drug carrier

Highly mesoporus spherical three dimensional (3D) ZnO nanoassemblies have been fabricated by a simple, facile soft-chemical approach. It has been observed that the mesoporous (average pore diameter of 28 nm) nanoscale assembly comprised of numerous nanocrystals of average size ∼20 nm is fairly stable, well-defined and discrete, with a hexagonal wurtzite structure. The drug-loading efficiency of the nanoassemblies was investigated using doxorubicin hydrochloride (DOX) as a model drug to evaluate their potential as a carrier system. The quenching of the fluorescence intensity as well as the change in band positions and spectra shapes strongly suggest the interaction of drug molecules with ZnO. More specifically, the present investigation discusses a method for entrapping drugs at sites capable of complexing with transition metal ions and suggests that drug release is dependent on the pH of the medium and externally applied ultrasound (continuous or pulsatile), as well as the nature of the materials which encapsulate the drug. In addition, nanoassemblies are biocompatible with HeLa cells and do not have toxic effects for further in vivo use. Specifically, a new paradigm for precise control of targeted, on-demand drug delivery using ultrasound irradiation is demonstrated.

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.

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.

Enhancement of magnetic heating efficiency in size controlled MFe2O4 (M = Mn, Fe, Co and Ni) nanoassemblies

The MFe2O4 magnetic nanoparticle nanoassemblies (MNNAs) have been synthesized via thermal decomposition of metal chloride in ethylene glycol (EG) in the presence of ethylenediamine (EDA). The size of the nanoassemblies is controlled in the range of 25–60 nm by manipulation of Fe-precursor mole content to ethylene glycol (EG) content and from 60 to 135 nm by using a bi-solvent mixture of ethylene glycol and polyethylene glycol (PEG-400). In this study, we demonstrate optimization of magnetic fluid heat activation by tailoring the size of MFe2O4 (M = Mn, Fe, Co and Ni) MNNAs. The densely packed nanocrystals within the MNNAs induce strong exchange as well as dipolar interactions between the nanocrystals, which increases the total magnetic moment for MNNAs. Additionally the magnetization (MS, magnetization in a field of 20 kOe) of MNNAs decreases in the order Mn > Fe > Co > Ni due to the cationic distribution of ions with varying magnetic moments in these spinel oxides. A sharp increase of heating efficiency for 25–60 nm assembled particles could be attributed to the collective Neel relaxation of nanocrystals within the assemblies and also due to high particle magnetic moment, which increases with the MNNAs size. Furthermore, among all the MFe2O4 nanoassemblies of various sizes, Fe3O4 MNNAs with an average diameter of 80 nm show an excellent SAR value of 646 W g−1 of Fe3O4 at 247 kHz with an applied AC magnetic field of 310 Oe, which is 4 times higher than that of the single domain assembled nanoparticles. The moderate anisotropy constant and high MS values of Fe3O4 MNNAs make it a most suitable candidate to produce the highest heating power. These magnetic MNNAs are efficient in killing the cancer cells by the application of an AC magnetic field even for a short treatment time of 30 min.

In-vitro evaluation of layered double hydroxide–Fe3O4 magnetic nanohybrids for thermo-chemotherapy

Among two-dimensional nanomaterials, layered double hydroxides (LDHs) are of great interest in biomedical applications due to their unique properties and layered structure. Superparamagnetic iron oxide nanoparticles (Fe3O4) are also well known for their tailorable properties, high magnetization values and biocompatibility. The objectives of our current work are to combine LDHs with magnetic nanoparticles in order to widen the horizons of their applications in cancer therapy. This work undertakes a facile chemical approach for the fabrication of Fe3O4-conjugated Mg–Al layered double hydroxide magnetic nanohybrids (MNHs). The successful fabrication of these MNHs was evident from X-ray diffraction analysis, infrared spectroscopy, X-ray photoelectron spectroscopy, and zeta potential measurements. These MNHs were explored as possible heating platforms for magnetic hyperthermia as well as drug-delivery vectors to cancer cells. A high degree of drug-loading efficiency (∼99%) for doxorubicin (Dox), with ∼90% release in high proton environments was observed. In addition, the nature of the host–drug interactions was systematically investigated by fluorescence spectroscopy. These MNHs were seen to be biocompatible with murine fibroblast (L929) and human cervical (HeLa) cell lines. To exemplify the therapeutic performances of Dox-loaded MNHs, the IC50 (50% inhibitory concentration) value was also evaluated against HeLa cells. Calorimetric measurements revealed the specific absorption rates of 98.4 and 73.5 W g−1 for Fe3O4 and MNHs, respectively. In addition, the MNHs acted as a “cut-off switch” to maintain the hyperthermic temperature. As hyperthermia agents, these MNHs showed that a 20 min exposure to an alternating current magnetic field (ACMF) is adequate to inhibit the proliferation of HeLa cells and decrease the cell population significantly. In conclusion, the results established that these MNHs open up avenues of much more effective anticancer therapy.

Dendrimer-conjugated iron oxide nanoparticles as stimuli-responsive drug carriers for thermally-activated chemotherapy of cancer

In recent years, functional nanomaterials have found an appreciable place in the understanding and treatment of cancer. This work demonstrates the fabrication and characterization of a new class of cationic, biocompatible, peptide dendrimers, which were then used for stabilizing and functionalizing magnetite nanoparticles for combinatorial therapy of cancer. The synthesized peptide dendrimers have an edge over the widely used PAMAM dendrimers due to better biocompatibility and negligible cytotoxicity of their degradation products. The surface engineering efficacy of the peptide dendrimers and their potential use as drug carriers were compared with their PAMAM counterparts. The peptide dendrimer was found to be as efficient as PAMAM dendrimers in its drug-carrying capacity, while its drug release profiles substantially exceeded those of PAMAMs. A dose-dependent study was carried out to assess their half maximal inhibitory concentration (IC50) in vitro with various cancer cell lines. A cervical cancer cell line that was incubated with these dendritic nanoparticles was exposed to alternating current magnetic field (ACMF) to investigate the effect of elevated temperatures on the live cell population. The DOX-loaded formulations, in combination with the ACMF, were also assessed for their synergistic effects on the cancer cells for combinatorial therapy. The results established the peptide dendrimer as an efficient alternative to PAMAM, which can be used successfully in biomedical applications.

Dendrimerized Magnetic Nanoparticles as Carriers for the Anticancer Compound, Epigallocatechin Gallate

Green tea polyphenols have attracted significant interest due to their promising therapeutic potential as antitumor agents. These include catechins that have been explored for various tumors with minimal side effects. This paper demonstrates the fabrication and characterization of dendrimerized magnetic nanoparticles, as delivery vectors for epigallocatechin gallate (EGCG). Glutamic acid-functionalized iron oxide nanoparticles (Glu-Fe3O4) were synthesized and modified with the polyethylene glycol polyamidoamine dendrimers of generations 3, 5, and 6. Nanoparticles were characterized by X-ray diffraction, electron microscopy, Fourier transform infrared spectroscopy, and vibrating sample magnetometry. In aqueous colloidal suspensions, they showed a rapid temperature increase under varying magnetic fields, suggesting their potential in chemothermal therapeutic applications. The loading efficiency of the dendrimerized nanoparticles was calculated to be 32.7%, 51.1%, and 56.4% for generations 3, 5, and 6, respectively. In acidic environments, a sustained drug release profile with an increasing but incomplete release was observed. Importantly, EGCG-loaded nanoparticles induced controlled cell death in human cervical cancer cells, demonstrating a 40% reduction in cell population over 24 h at the highest concentration used, with a linear dose-response.