Formation of Core-Shell Nanoparticles Composed of Magnetite and Samarium Oxide in Magnetospirillum magneticum Strain RSS-1.

Magnetotactic bacteria (MTB) synthesize magnetosomes composed of membrane-enveloped magnetite (Fe3O4) or greigite (Fe3S4) particles in the cells. Recently, several studies have shown some possibilities of controlling the biomineralization process and altering the magnetic properties of magnetosomes by adding some transition metals to the culture media under various environmental conditions. Here, we successfully grow Magnetospirillum magneticum strain RSS-1, which are isolated from a freshwater environment, and find that synthesis of magnetosomes are encouraged in RSS-1 in the presence of samarium and that each core magnetic crystal composed of magnetite is covered with a thin layer of samarium oxide (Sm2O3). The present results show some possibilities of magnetic recovery of transition metals and synthesis of some novel structures composed of magnetic particles and transition metals utilizing MTB.

Highly versatile SPION encapsulated PLGA nanoparticles as photothermal ablators of cancer cells and as multimodal imaging agents.

We have designed versatile polymeric nanoparticles with cancer cell specific targeting capabilities via aptamer conjugation after the successful encapsulation of curcumin and superparamagnetic iron oxide nanoparticles (SPIONs) inside a PLGA nanocapsule. These targeted nanocomposites were selectively taken up by tumor cells, under in vitro conditions, demonstrating the effectiveness of the aptamer targeting mechanism. Moreover, the nanocomposite potentially functioned as efficient multiprobes for optical, magnetic resonance imaging (MRI) and photoacoustic imaging contrast agents in the field of cancer diagnostics. The hyperthermic ability of these nanocomposites was mediated by SPIONs upon NIR-laser irradiation. In vitro cytotoxicity was shown by curcumin-loaded nanoparticles as well as the photothermal ablation of cancer cells mediated by the drug-encapsulated nanocomposite demonstrated the potential therapeutic effect of the nanocomposite. In short, we portray the aptamer-conjugated nanocomposite as a multimodal material capable of serving as a contrast agent for MR, photoacoustic and optical imaging. Furthermore, the nanocomposite functions as a targetable drug nanocarrier and a NIR-laser inducible hyperthermic material that is capable of ablating PANC-1 and MIA PaCa-2 cancer cell lines.

Synthesis of magnetic alloy-filling carbon nanoparticles in super-critical benzene irradiated with an ultraviolet laser.

Magnetic nanoparticles are of great importance particularly in the field of biomedicine as well as nanotechnology and nano materials science and technology. Here, we synthesise magnetic alloy-filling carbon nanoparticles (MA@C NPs) via the following two-step procedure; (1) Irradiation of a laser beam of 266 nm wavelength into super-critical benzene, in which both ferrocene and cobaltocene are dissolved, at 290 °C; and (2) annealing of the particles at 600 and 800 °C. We find that the core particles are composed of cobalt (Co), iron (Fe) and oxygen (O) and covered with carbon layers. The structure of the core particles as-synthesised, and annealed at 600 and 800 °C, is, respectively, amorphous, CoFe2O4 and FeCo. We also investigate the viability of L929 cells in the presence of MA@C NPs and find that there is no serious advert effect of the MA@C NPs on the cell viability thanks to the carbon layers covering the core particles. The magnetic properties are well characterised. The saturation and remnant magnetisation and coercivity increase and as a result, the hyperthermic efficiency becomes higher with an increase in the annealing temperature. The further modification of the surface of the present particles with several functional molecules becomes easier due to the carbon layers, which makes the present particles more valuable. It is therefore supposed that the presently synthesised MA@C NPs may well be utilised for nanotechnology-based biomedical engineering; e.g., nano bioimaging, nano hyperthermia and nano surgery.

Dual mode of cancer cell destruction for pancreatic cancer therapy using Hsp90 inhibitor loaded polymeric nano magnetic formulation.

Heat Shock Protein 90 (Hsp90) has been extensively explored as a potential drug target for cancer therapies. 17- N-allylamino- 17-demethoxygeldanamycin (17AAG) was the first Hsp90 inhibitor to enter clinical trials for cancer therapy. However, native drug is being shown to have considerable anticancer efficacy against pancreatic cancer when used in combination therapy regime. Further, magnetic hyperthermia has shown to have promising effects against pancreatic cancer in combination with known cyto-toxic drugs under both target and non-targeted scenarios. Hence, in order to enhance the efficacy of 17AAG against pancreatic cancer, we developed poly (lactic-co-glycolic acid) (PLGA) coated, 17AAG and Fe3O4 loaded magnetic nanoparticle formulations by varying the relative concentration of polymer. We found that polymer concentration affects the magnetic strength and physicochemical properties of formulation. We were also able to see that our aqueous dispensable formulations were able to provide anti-pancreatic cancer activity for MIA PaCa-2 cell line in dose and time dependent manner in comparison to mice fibroblast cell lines (L929). Moreover, the in-vitro magnetic hyperthermia against MIA PaCa-2 provided proof principle that our 2-in-1 particles may work against cancer cell lines effectively.

Composition, Electronic and Magnetic Investigation of the Encapsulated ZnFe2O 4 Nanoparticles in Multiwall Carbon Nanotubes Containing Ni Residuals.

We report investigation on properties of multiwall carbon nanotubes (mCNTs) containing Ni residuals before and after encapsulation of zinc ferrite nanoparticles. The pristine tubes exhibit metallic character with a 0.3 eV reduction in the work function along with ferromagnetic behavior which is attributed to the Ni residuals incorporated during the preparation of tubes. Upon encapsulation of zinc ferrite nanoparticles, 0.5 eV shift in Fermi level position and a reduction in both the π band density of state along with a change in the hybridized sp(2)/sp(3) ratio of the tubes from 2.04 to 1.39 are observed. As a result of the encapsulation, enhancement in the σ bands density of state and coating of the zinc ferrite nanoparticles by the internal layers of the CNTs in the direction along the tube axis is observed. Furthermore, Ni impurities inside the tubes are attracted to the encapsulated zinc ferrite nanoparticles, suggesting the possibility of using these particles as purifying agents for CNTs upon being synthesized using magnetic catalyst particles. Charge transfer from Ni/mCNTs to the ZnFe2O4 nanoparticles is evident via reduction of the density of states near the Fermi level and a 0.3 eV shift in the binding energy of C 1 s core level ionization. Furthermore, it is demonstrated that encapsulated zinc ferrite nanoparticles in mCNTs resulted in two interacting sub-systems featured by distinct blocking temperatures and enhanced magnetic properties; i.e., large coercivity of 501 Oe and saturation magnetization of 2.5 emu/g at 4 K.

Effect of Polyethylene Glycol on the Formation of Magnetic Nanoparticles Synthesized by Magnetospirillum magnetotacticum MS-1.

Magnetotactic bacteria (MTB) synthesize intracellular magnetic nanocrystals called magnetosomes, which are composed of either magnetite (Fe3O4) or greigite (Fe3S4) and covered with lipid membranes. The production of magnetosomes is achieved by the biomineralization process with strict control over the formation of magnetosome membrane vesicles, uptake and transport of iron ions, and synthesis of mature crystals. These magnetosomes have high potential for both biotechnological and nanotechnological applications, but it is still extremely difficult to grow MTB and produce a large amount of magnetosomes under the conventional cultural conditions. Here, we investigate as a first attempt the effect of polyethylene glycol (PEG) added to the culture medium on the increase in the yield of magnetosomes formed in Magnetospirillum magnetotacticum MS-1. We find that the yield of the formation of magnetosomes can be increased up to approximately 130 % by adding PEG200 to the culture medium. We also measure the magnetization of the magnetosomes and find that the magnetosomes possess soft ferromagnetic characteristics and the saturation mass magnetization is increased by 7 %.

Multi-stimuli responsive Cu2S nanocrystals as trimodal imaging and synergistic chemo-photothermal therapy agents.

A size and shape tuned, multifunctional metal chalcogenide, Cu2S-based nanotheranostic agent is developed for trimodal imaging and multimodal therapeutics against brain cancer cells. This theranostic agent was highly efficient in optical, photoacoustic and X-ray contrast imaging systems. The folate targeted NIR-responsive photothermal ablation in synergism with the chemotherapeutic action of doxorubicin proved to be a rapid precision guided cancer-killing module. The multi-stimuli, i.e., pH-, thermo- and photo-responsive drug release behavior of the nanoconjugates opens up a wider corridor for on-demand triggered drug administration. The simple synthesis protocol, combined with the multitudes of interesting features packed into a single nanoformulation, clearly demonstrates the competing role of this Cu2S nanosystem in future cancer treatment strategies.

Extremophilic polysaccharide nanoparticles for cancer nanotherapy and evaluation of antioxidant properties.

Polysaccharides that show finest bioactivities and physicochemical properties are always promising for bionanoscience applications. Mauran is such a macromolecule extracted from halophilic bacterium, Halomonas maura for biotechnology and nanoscience applications. Antioxidant properties of MR/CH nanoparticles were studied using biochemical assays to prove the versatility of these test nanoparticles for biomedical applications. Here, we demonstrate the prospects of extremophilic polysaccharide, mauran based nanoparticles for scavenging reactive oxygen species in both in vitro and ex vivo conditions. 5-fluorouracil loaded MR/CH nanoparticles were tested for anticancer proliferation and compared their therapeutic efficiency using breast adenocarcinoma and glioma cells. Fluorescently labeled nanoparticles were employed to show the cellular uptake of these nanocarriers using confocal microscopic imaging and flow cytometry.

FITC/suramin harboring silica nanoformulations for cellular and embryonic imaging/anti-angiogenic theranostics.

The in vitro and in vivo uptake, toxicological analysis and anti-angiogenic theranostic prospect of FITC loaded (FITC-Si) and suramin loaded (Sur-Si) silica nanoparticles are presented. FITC/suramin encapsulated silica nanoparticles (NPs) with an average size of <30 nm were synthesized. The uptake of FITC-Si by human umbilical vein endothelial cells (HuVECs) (in vitro) and by early stage medaka embryos (in vivo) was monitored by fluorescence microscopy. The nanoformulation was found to be biocompatible with both cells and embryos. The cytotoxicity analysis, tubulogenesis and migration assay confirmed the anti-angiogenic potential of Sur-Si NPs in HuVECs. The imaging of medaka embryos exposed to FITC-Si, their survival and hatching rate and biocompatibility post FITC-Si exposure were documented. The in vivo drug delivery mediated anti-angiogenic potential of Sur-Si NPs was assessed by survival and hatching rate analysis along with morphological indicators. At higher concentrations, Sur-Si proved lethal to embryos, whereas at lower concentrations it was rather an efficient anti-angiogenic formulation leading to malformed vasculogenesis and inhibited intersegmental vessel formation in an efficient dose dependent mode. The results indicate the potential application of such nanoformulation in future anti-angiogenic theranostics.

Structurally distinct hybrid polymer/lipid nanoconstructs harboring a type-I ribotoxin as cellular imaging and glioblastoma-directed therapeutic vectors.

A nanoformulation composed of a ribosome inactivating protein-curcin and a hybrid solid lipid nanovector has been devised against glioblastoma. The structurally distinct nanoparticles were highly compatible to human endothelial and neuronal cells. A sturdy drug release from the particles, recorded upto 72 h, was reflected in the time-dependent toxicity. Folate-targeted nanoparticles were specifically internalized by glioma, imparting superior toxicity and curbed an aggressively proliferating in vitro 3D cancer mass in addition to suppressing the anti-apoptotic survivin and cell matrix protein vinculin. Combined with the imaging potential of the encapsulated dye, the nanovector emanates as a multifunctional anti-cancer system.

Bacterial exopolysaccharide based magnetic nanoparticles: a versatile nanotool for cancer cell imaging, targeted drug delivery and synergistic effect of drug and hyperthermia mediated cancer therapy.

Microbial exopolysaccharides (EPSs) are highly heterogeneous polymers produced by fungi and bacteria that have garnered considerable attention and have remarkable potential in various fields, including biomedical research. The necessity of biocompatible materials to coat and stabilize nanoparticles is highly recommended for successful application of the same in biomedical regime. In our study we have coated magnetic nanoparticles (MNPs) with two bacterial EPS-mauran (MR) and gellan gum (GG). The biocompatibility of EPS coated MNPs was enhanced and we have made it multifunctional by attaching targeting moiety, folate and with encapsulation of a potent anticancerous drug, 5FU. We have conjugated an imaging moiety along with nanocomposite to study the effective uptake of nanoparticles. It was also observed that the dye labeled folate targeted nanoparticles could effectively enter into cancer cells and the fate of nanoparticles was tracked with Lysotracker. The biocompatibility of EPS coated MNPs and synergistic effect of magnetic hyperthermia and drug for enhanced antiproliferation of cancer cells was also evaluated. More than 80% of cancer cells was killed within a period of 60 min when magnetic hyperthermia (MHT) was applied along with drug loaded EPS coated MNPs, thus signifying the combined effect of drug loaded MNPs and MHT. Our results suggests that MR and GG coated MNPs exhibited excellent biocompatibility with low cell cytotoxicity, high therapeutic potential, and superparamagnetic behavior that can be employed as prospective candidates for bacterial EPS based targeted drug delivery, cancer cell imaging and for MHT for killing cancer cells within short period of time.

Quantum dot tailored to single wall carbon nanotubes: a multifunctional hybrid nanoconstruct for cellular imaging and targeted photothermal therapy.

Hybrid nanomaterial based on quantum dots and SWCNTs is used for cellular imaging and photothermal therapy. Furthermore, the ligand conjugated hybrid system (FaQd@CNT) enables selective targeting in cancer cells. The imaging capability of quantum dots and the therapeutic potential of SWCNT are available in a single system with cancer targeting property. Heat generated by the system is found to be high enough to destroy cancer cells.

Curcumin and 5-fluorouracil-loaded, folate- and transferrin-decorated polymeric magnetic nanoformulation: a synergistic cancer therapeutic approach, accelerated by magnetic hyperthermia.

The efficient targeting and therapeutic efficacy of a combination of drugs (curcumin and 5-Fluorouracil [5FU]) and magnetic nanoparticles encapsulated poly(D,L-lactic-co-glycolic acid) nanoparticles, functionalized with two cancer-specific ligands are discussed in our work. This multifunctional, highly specific nanoconjugate resulted in the superior uptake of nanoparticles by cancer cells. Upon magnetic hyperthermia, we could harness the advantages of incorporating magnetic nanoparticles that synergistically acted with the drugs to destroy cancer cells within a very short period of time. The remarkable multimodal efficacy attained by this therapeutic nanoformulation offers the potential for targeting, imaging, and treatment of cancer within a short period of time (120 minutes) by initiating early and late apoptosis.

Type 1 ribotoxin-curcin conjugated biogenic gold nanoparticles for a multimodal therapeutic approach towards brain cancer.

BACKGROUND: Gliomas have been termed recurrent cancers due to their highly aggressive nature. Their tendency to infiltrate and metastasize has posed significant roadblocks to in attaining fool proof treatment solutions. An initiative to curb such a scenario was successfully demonstrated in vitro, utilizing a multi-conceptual gold nanoparticle based photo-thermal and drug combination therapy. METHODS: Gold nanoparticles (Au NPs) were synthesized with a highly environmentally benign process. The Au NPs were PEGylated and conjugated with folate and transferrin antibody to achieve a dual targeted nano-formulation directed towards gliomas. Curcin, a type 1 ribosome inactivating protein, was attached to the Au NPs as the drug candidate, and its multifarious toxic aspects analyzed in vitro. NIR photo-thermal properties of the Au nano-conjugates were studied to selectively ablate the glioma cancer colonies. RESULTS: Highly cyto-compatible, 10-15nm Au NP conjugates were synthesized with pronounced specificity towards gliomas. Curcin was successfully conjugated to the Au NPs with pH responsive drug release. Prominent toxic aspects of curcin, such as ROS generation, mitochondrial and cytoskeletal destabilization were witnessed. Excellent photo-thermal ablation properties of gold nanoparticles were utilized to completely disrupt the cancer colonies with significant precision. CONCLUSION: The multifunctional nanoconjugate projects its competence in imparting complete arrest of the future proliferation or migration of the cancer mass. GENERAL SIGNIFICANCE: With multifunctionality the essence of nanomedicine in recent years, the present nanoconjugate highlights itself as a viable option for a multimodal treatment option for brain cancers and the like.

Fluorinated graphene oxide; a new multimodal material for biological applications.

Fluorinated graphene oxide (FGO) is reported for the first time as a magnetically responsive drug carrier that can serve both as a magnetic resonance imaging (MRI) and photoacoustic contrast agent, under preclinical settings, and as a type of photothermal therapy. Its hydrophilic nature facilitates biocompatibility. FGO as a broad wavelength absorber, with high charge transfer and strong non-linear scattering is optimal for NIR laser-induced hyperthermia.

Accelerated killing of cancer cells using a multifunctional single-walled carbon nanotube-based system for targeted drug delivery in combination with photothermal therapy.

The photothermal effect of single-walled carbon nanotubes (SWCNTs) in combination with the anticancer drug doxorubicin (DOX) for targeting and accelerated destruction of breast cancer cells is demonstrated in this paper. A targeted drug-delivery system was developed for selective killing of breast cancer cells with polyethylene glycol biofunctionalized and DOX-loaded SWCNTs conjugated with folic acid. In our work, in vitro drug-release studies showed that the drug (DOX) binds at physiological pH (pH 7.4) and is released only at a lower pH, ie, lysosomal pH (pH 4.0), which is the characteristic pH of the tumor environment. A sustained release of DOX from the SWCNTs was observed for a period of 3 days. SWCNTs have strong optical absorbance in the near-infrared (NIR) region. In this special spectral window, biological systems are highly transparent. Our study reports that under laser irradiation at 800 nm, SWCNTs exhibited strong light-heat transfer characteristics. These optical properties of SWCNTs open the way for selective photothermal ablation in cancer therapy. It was also observed that internalization and uptake of folate-conjugated NTs into cancer cells was achieved by a receptor-mediated endocytosis mechanism. Results of the in vitro experiments show that laser was effective in destroying the cancer cells, while sparing the normal cells. When the above laser effect was combined with DOX-conjugated SWCNTs, we found enhanced and accelerated killing of breast cancer cells. Thus, this nanodrug-delivery system, consisting of laser, drug, and SWCNTs, looks to be a promising selective modality with high treatment efficacy and low side effects for cancer therapy.

Activity of lipase and chitinase immobilized on superparamagnetic particles in a rotational magnetic field.

We immobilize hydrolases such as lipase and chitinase on superparamagnetic particles, which are subjected to a rotational magnetic field, and measure the activities of the enzymes. We find that the activities of lipase and chitinase increase in the rotational magnetic field compared to those in the absence of a magnetic field and reach maximum at certain frequencies. The present methodology may well be utilized for the design and development of efficient micro reactors and micro total analysis systems (µ-TASs).

Biocompatible nanofibers based on extremophilic bacterial polysaccharide, Mauran from Halomonas maura.

Extremophilic bacterial polysaccharide based biocompatible nanofibers were produced for the first time via electrospinning technique. Mauran (MR), an extremophilic sulfated exopolysaccharide was extracted from moderately halophilic bacterium, Halomonas maura and characterized for the application of nanofiber synthesis. Thin-uniform MR nanofibers were produced using homogenous solutions of poly (vinyl alcohol) (PVA) blended with different concentrations of MR. Characterization of complex MR/PVA nanofibers were performed using scanning electron microscope and analyzed for the cytotoxicity using mouse fibroblast cells as well as mesenchymal stem cells. An average of 120 nm sized nanofibers were produced and tested for an enhanced cell growth under in vitro conditions in comparison with control. MR and MR/PVA nanofibers were found to be an excellent biomaterial for the migration, proliferation and differentiation of mammalian cells, which was confirmed by cell adhesion studies and confocal microcopy. Interestingly, biological and physicochemical properties of MR hasten the application of MR based nanofibers for various biomedical applications like tissue engineering and drug delivery.

Multifunctional carboxymethyl cellulose-based magnetic nanovector as a theragnostic system for folate receptor targeted chemotherapy, imaging, and hyperthermia against cancer.

A multifunctional biocompatible nanovector based on magnetic nanoparticle and carboxymethyl cellulose (CMC) was developed. The nanoparticles have been characterized using TEM, SEM, DLS, FT-IR spectra, VSM, and TGA studies. We found that the synthesized carboxymethyl cellulose magnetic nanoparticles (CMC MNPs) were spherical in shape with an average size of 150 nm having low aggregation and superparamagnetic properties. We found that the folate-tagged CMC MNPs were delivered to cancer cells by a folate-receptor-mediated endocytosis mechanism. 5-FU was encapsulated as a model drug for delivering cytotoxicity, and we could demonstrate the sustained release of 5-FU. It was also observed that the FITC-labeled CMC MNPs could effectively enter cells, and the fate of nanoparticles was tracked with Lysotracker. The CMC MNPs could induce significant cell death when an alternating magnetic field was applied. These results indicate that the multifunctional CMC MNPs possess a high drug loading efficiency and high biocompatibility and with low cell cytotoxicity and can be considered to be promising candidates for CMC-based targeted drug delivery, cellular imaging, and magnetic hyperthermia (MHT).

Synergistic targeting of cancer and associated angiogenesis using triple-targeted dual-drug silica nanoformulations for theragnostics.

The targeting and therapeutic efficacy of dye- and dual-drug-loaded silica nanoparticles, functionalized with triple targeting ligands specific towards cancer and neoangiogenesis simultaneously, are discussed. This synergized, high-precision, multitarget concept culminates in an elevated uptake of nanoparticles by cancer and angiogenic cells with amplified proficiency, thereby imparting superior therapeutic efficacy against breast cancer cells and completely disabling the migration and angiogenic sprouting ability of activated endothelial cells. The exceptional multimodal efficiency achieved by this single therapeutic nanoformulation holds promise for the synergistic targeting and treatment of the yet elusive cancer and its related angiogenesis in a single, lethal shot.