Nontoxic In Vivo Clearable Nanoparticle Clusters for Theranostic Applications.

Disintegrable inorganic nanoclusters (GIONs) with gold seed (GS) coating of an iron oxide core with a primary nanoparticle size less than 6 nm were prepared for theranostic applications. The GIONs possessed a broad near-infrared (NIR) absorbance at ∼750 nm because of plasmon coupling between closely positioned GSs on the iron oxide nanoclusters (ION) surface, in addition to the ∼513 nm peak corresponding to the isolated GS. The NIR laser-triggered photothermal response of GIONs was found to be concentration-dependent with a temperature rise of ∼8.5 and ∼4.5 °C from physiological temperature for 0.5 and 0.25 mg/mL, respectively. The nanoclusters were nonhemolytic and showed compatibility with human umbilical vein endothelial cells up to a concentration of 0.7 mg/mL under physiological conditions. The nanoclusters completely disintegrated at a lysosomal pH of 5.2 within 1 month. With an acute increase of over 400% intracellular reactive oxygen species soon after γ-irradiation and assistance from Fenton reaction-mediated supplemental oxidative stress, GION treatment in conjunction with radiation killed ∼50% of PLC/PRF/5 hepatoma cells. Confocal microscopy images of these cells showed significant cytoskeletal and nuclear damage from radiosensitization with GIONs. The cell viability further decreased to ∼10% when they were sequentially exposed to the NIR laser followed by γ-irradiation. The magnetic and optical properties of the nanoclusters enabled GIONs to possess a T2 relaxivity of ∼223 mM-1 s-1and a concentration-dependent strong photoacoustic signal toward magnetic resonance and optical imaging. GIONs did not incur any organ damage or evoke an acute inflammatory response in healthy C57BL/6 mice. Elemental analysis of various organs indicated differential clearance of gold and iron via both renal and hepatobiliary routes.

Polymeric Core-Shell Combinatorial Nanomedicine for Synergistic Anticancer Therapy.

Core-shell nanostructures are promising platforms for combination drug delivery. However, their complicated synthesis process, poor stability, surface engineering, and low biocompatibility are major hurdles. Herein, a carboxymethyl chitosan-coated poly(lactide-co-glycolide) (cmcPLGA) core-shell nanostructure is prepared via a simple one-step nanoprecipitation self-assembly process. Engineered core-shell nanostructures are tested for combination delivery of loaded docetaxel and doxorubicin in a cancer-mimicked environment. The drugs are compartmentalized in a shell (doxorubicin, Dox) and a core (docetaxel, Dtxl) with loading contents of ∼1.2 and ∼2.06%, respectively. Carboxymethyl chitosan with both amine and carboxyl groups act as a polyampholyte in diminishing ζ-potential of nanoparticles from fairly negative (-13 mV) to near neutral (-2 mV) while moving from a physiological pH (7.4) to an acidic tumor pH (6) that can help the nanoparticles to accumulate and release the drug on-site. The dual-drug formulation was found to carry a clinically comparable 1.7:1 weight ratio of Dtxl/Dox, nanoengineered for the sequential release of Dox followed by Dtxl. Single and engineered combinatorial nanoformulations show better growth inhibition toward three different cancer cells compared to free drug treatment. Importantly, Dox-Dtxl cmcPLGA nanoparticles scored synergism with combination index values between 0.2 and 0.3 in BT549 (breast ductal carcinoma), PC3 (prostate cancer), and A549 (lung adenocarcinoma) cell lines, demonstrating significant cell growth inhibition at lower drug concentrations as compared to single-drug control groups. The observed promising performance of dual-drug formulation is due to the G2/M phase arrest and apoptosis.

Biocompatibility and therapeutic evaluation of magnetic liposomes designed for self-controlled cancer hyperthermia and chemotherapy.

Magnetic liposome-mediated combined chemotherapy and hyperthermia is gaining importance as an effective therapeutic modality for cancer. However, control and maintenance of optimum hyperthermia are major challenges in clinical settings due to the overheating of tissues. To overcome this problem, we developed a novel magnetic liposomes formulation co-entrapping a dextran coated biphasic suspension of La0.75Sr0.25MnO3 (LSMO) and iron oxide (Fe3O4) nanoparticles for self-controlled hyperthermia and chemotherapy. However, the general apprehension about biocompatibility and safety of the newly developed formulation needs to be addressed. In this work, in vitro and in vivo biocompatibility and therapeutic evaluation studies of the novel magnetic liposomes are reported. Biocompatibility study of the magnetic liposomes formulation was carried out to evaluate the signs of preliminary systemic toxicity, if any, following intravenous administration of the magnetic liposomes in Swiss mice. Therapeutic efficacy of the magnetic liposomes formulation was evaluated in the fibrosarcoma tumour bearing mouse model. Fibrosarcoma tumour-bearing mice were subjected to hyperthermia following intratumoral injection of single or double doses of the magnetic liposomes with or without chemotherapeutic drug paclitaxel. Hyperthermia (three spurts, each at 3 days interval) with drug loaded magnetic liposomes following single dose administration reduced the growth of tumours by 2.5 fold (mean tumour volume 2356 ± 550 mm3) whereas the double dose treatment reduced the tumour growth by 3.6 fold (mean tumour volume 1045 ± 440 mm3) compared to their corresponding control (mean tumour volume 3782 ± 515 mm3). At the end of the tumour efficacy studies, the presence of MNPs was studied in the remnant tumour tissues and vital organs of the mice. No significant leaching or drainage of the magnetic liposomes during the study was observed from the tumour site to the other vital organs of the body, suggesting again the potential of the novel magnetic liposomes formulation for possibility of developing as an effective modality for treatment of drug resistant or physiologically vulnerable cancer.

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 PAMAM's. 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.

Electrochemical Method To Prepare Graphene Quantum Dots and Graphene Oxide Quantum Dots.

In this study, we present the preparation of graphene quantum dots (GQDs) and graphene oxide quantum dots (GOQDs). GQDs/GOQDs are prepared by an easy electrochemical exfoliation method, in which two graphite rods are used as electrodes. The electrolyte used is a combination of citric acid and alkali hydroxide in water. Four types of quantum dots, GQD1-GQD4, are prepared by varying alkali hydroxide concentration in the electrolyte, while keeping the citric acid concentration fixed. Variation of alkali hydroxide concentration in the electrolyte results in the production of GOQDs. Balanced reaction of citric acid and alkali hydroxide results in the production of GQDs (GQD3). However, three variations in alkali hydroxide concentration result in GOQDs (GQD1, GQD2, and GQD4). GOQDs show tunable oxygen functional groups, which are confirmed by X-ray photoelectron spectroscopy. GQDs/GOQDs show absorption in the UV region and show excitation-dependent photoluminescence behavior. The obtained average size is 2-3 nm, as revealed by transmission electron microscopy. X-ray diffraction peak at around 10° and broad D band peak at 1350 cm-1 in Raman spectra confirm the presence of oxygen-rich functional groups on the surface of GOQDs. These GQDs and GOQDs show blue to green luminescence under 365 nm UV irradiation.

NIR absorbing Au nanoparticle decorated layered double hydroxide nanohybrids for photothermal therapy and fluorescence imaging of cancer cells.

Among inorganic nanomaterials, layered double hydroxides (LDHs) and gold nanoparticles (Au NPs) have received great attention in nanobiomedicine due to their unique properties. In this work, we have designed a nanohybrid of an LDH with Au NPs (LDH-Au) in order to use it for photothermal therapy, and optical and fluorescence imaging of cancer cells. The structural characteristics of the nanohybrid are investigated using X-ray diffraction, infrared spectroscopy, electron microscopy and elemental analyses. The extinction spectra of the nanohybrid exhibits broad absorption ranging from the visible to near infrared (NIR) region (500-1000 nm). The photothermal activity of the nanohybrid is explored using NIR laser irradiation. The electric field enhancement in the nanohybrid due to the interaction of Au NPs on the LDH is speculated through finite-difference time-domain (FDTD) calculations. The LDH-Au nanohybrid is found to be biocompatible with normal murine fibroblast (L929), human breast cancer (MCF-7) and cervical cancer (HeLa) cell lines up to a concentration of 1 mg mL-1. The nanohybrid is explored for in vitro photothermal therapy of MCF-7 and HeLa cell lines. As a photothermal agent, the nanohybrid shows that 10 min exposure to an 808 nm laser (500 mW) is adequate to inhibit about 70% of cancer cells. Further, the nanohybrid is tagged with FITC to study both optical and fluorescence imaging with MCF-7 cell lines. The results demonstrate that the LDH-Au nanohybrid provides an innovative approach to photothermal therapy, and optical and fluorescence imaging of cancer cells.

Targeted Magnetic Liposomes Loaded with Doxorubicin.

Targeted delivery systems for anticancer drugs are urgently needed to achieve maximum therapeutic efficacy by site-specific accumulation and thereby minimizing adverse effects resulting from systemic distribution of many potent anticancer drugs. We have prepared folate receptor-targeted magnetic liposomes loaded with doxorubicin, which are designed for tumor targeting through a combination of magnetic and biological targeting. Furthermore, these liposomes are designed for hyperthermia-induced drug release to be mediated by an alternating magnetic field and to be traceable by magnetic resonance imaging (MRI). Here, detailed preparation and relevant characterization techniques of targeted magnetic liposomes encapsulating doxorubicin are described.

Magnetic core-shell hybrid nanoparticles for receptor targeted anti-cancer therapy and magnetic resonance imaging.

Hybrid nanoparticles with magnetic poly (lactide-co-glycolide) (PLGA) nanoparticle 'core', surface modified with folate-chitosan (fol-cht) conjugate 'shell' are evaluated as simultaneous anti-cancer therapeutic and MRI contrast agent. The fol-cht conjugate is prepared using carbodiimide crosslinking chemistry at an optimized folate to amine (chitosan) molar ratio for further coating on PLGA nanoparticles loaded with docetaxel and well packed super paramagnetic iron oxide nanoparticles (SPIONs). Apart from possessing a targeting moiety, the coating provides a physical barrier to avoid undesired burst release of drug and also imparts sensitivity to acidic pH, due to protonated amine group dependent decondensation of the coating and subsequent drug release. The biocompatible hybrid nanoparticles provide receptor targeted docetaxel and SPION delivery for anti-cancer therapy and magnetic resonance (MR) imaging respectively, as tested in both folate receptor positive and negative cancer cells. Enhancement in nanoparticle uptake by folate receptor positive oral cancer cells caused significant increase in docetaxel mediated cytotoxicity. While polymeric encapsulation and fol-cht coating negatively affects the magnetic property of iron oxide nanoparticles, their aggregation in the core, shortened the overall T2 relaxation time thereby enhancing the nanoparticle relaxivity to provide better in vitro MR imaging.

Assessing Therapeutic Potential of Magnetic Mesoporous Nanoassemblies for Chemo-Resistant Tumors.

Smart drug delivery system with strategic drug distribution is the future state-of-the-art treatment for any malignancy. To investigate therapeutic potential of such nanoparticle mediated delivery system, we examined the efficacy of dual drug-loaded, pH and thermo liable lipid coated mesoporous iron oxide-based magnetic nanoassemblies (DOX:TXL-LMMNA) in mice bearing both drug sensitive (A2780(S)) and drug resistant (A2780-CisR) ovarian cancer tumor xenografts. In presence of an external AC magnetic field (ACMF), DOX:TXL-LMMNA particles disintegrate to release encapsulated drug due to hyperthermic temperatures (41-45 ºC). In vivo bio distribution study utilizing the optical and magnetic properties of DOX:TXL-LMMNA particles demonstrated minimum organ specific toxicity. Noninvasive bioluminescence imaging of mice bearing A2780(S) tumors and administered with DOX-TXL-LMMNA followed by the application of ACMF revealed 65% less luminescence signal and 80% mice showed complete tumor regression within eight days. A six months follow-up study revealed absence of relapse in 70% of the mice. Interestingly, the A2780-CisR tumors which did not respond to drug alone (DOX:TXL) showed 80% reduction in luminescence and tumor volume with DOX:TXL-LMMNA after thermo-chemotherapy within eight days. Cytotoxic effect of DOX:TXL-LMMNA particles was more pronounced in A2780-CisR cells than in their sensitive counterpart. Thus these novel stimuli sensitive nanoassemblies hold great promise for therapy resistant malignancies and future clinical applications.

Protein-Poly(amino acid) Nanocore-Shell Mediated Synthesis of Branched Gold Nanostructures for Computed Tomographic Imaging and Photothermal Therapy of Cancer.

Anisotropic noble metal nanoparticles especially branched gold nanoparticles with a large absorption cross-section and high molar extinction coefficient have promising applications in biomedical field. However, sophisticated and cumbersome methodologies of synthesis along with toxic precursors pose serious concern for its use. Herein, we report the synthesis of branched gold nanostructures from protein (albumin) nanoparticles by a simple reduction method. Albumin nanoparticles were synthesized by a modified desolvation technique with poly-l-arginine (cationic poly amino acid) substituting the conventional toxic cross-linker, glutaraldehyde. In silico molecular docking was carried out to study the interaction of poly-l-arginine with albumin which revealed its binding to Pocket 1B of the A-chain of albumin. The poly-l-arginine-albumin core-shell nanoparticles of ∼100 nm in size served as a base for attachment of gold ions and its reduction to form 140 nm sized branched gold nanostructures conjugated with glutathione. These gold nanostructures exhibited near-infrared absorption λmax at 800 nm with extreme compatibility toward non cancerous (NIH 3T3), oral epithelial carcinoma (KB) cell lines, and human blood (red blood cells, platelets, and coagulation mechanisms) even up to a high concentration of 250 µg/mL. These structures demonstrated superior computed tomographic (CT) contrast ability and marked photothermal cytotoxicity on KB cells. This study reports for the first time a method to develop blood and cell compatible branched gold nanostructures from protein nanoparticles as a dual CT diagnostic and photothermal therapeutic agent.

Mechanism of Anti-Cancer Activity of Benomyl Loaded Nanoparticles in Multidrug Resistant Cancer Cells.

Polymeric chitosan-poly(D,L-lactide-co-glycolide) nanoparticles loaded with benomyl as anticancer drug formulation against multidrug-resistant EMT6/AR1 cells were synthesized by amine-carboxylate reaction. Using transmission electron microscopy, the average size of chitosan-poly(D,L-lactide-co-glycolide) nanoparticles and benomyl-encapsulated polymeric chitosan-poly(D,L-lactide-co-glycolide) nanoparticles was estimated to be 155 ± 20 nm and 160 ± 25 nm, respectively. Fourier transform infrared spectroscopy revealed that poly(D,L-lactide-co-glycolide) and chitosan are linked by covalent bonds. Zeta potentials of benomyl-encapsulated polymeric chitosan-poly(D,L-lactide-co-glycolide) nanoparticles at pH 4, 7.2, and 10 were 30 ± 1.8, 19 ± 0.65, and -22 ± 0.15 mV, respectively, indicating the formation of stable, hydrophilic nanoparticles. The release of benomyl from benomyl-encapsulated polymeric chitosan-poly(D,L-lactide-co-glycolide) nanoparticles followed pH-dependent kinetics. The uptake of fluorescein isothiocyanate-labeled chitosan-poly(D,L-lactide-co-glycolide) nanoparticles was concentration-dependent in both MCF-7 and multidrug-resistant EMT6/AR1 cells. EMT6/AR1 cells showed 10-fold higher resistance to benomyl compared to MCF-7 cells; in contrast, benomyl-encapsulated polymeric chitosan-poly(D,L-lactide-co-glycolide) nanoparticles effectively inhibited proliferation of MCF-7 and EMT6/AR1 cells with a half-maximal inhibitory concentration of 4 ± 0.5 and 9 ± 0.5 pM, respectively. In the presence of a P-glycoprotein inhibitor, the activity of benomyl was increased, suggesting that benomyl is a substrate for P-glycoprotein. Further, benomyl-encapsulated polymeric chitosan-poly(D,L-lactide-co-glycolide) nanoparticles depoly-merized microtubules both in interphase and mitosis. It blocked cell cycle progression at G2/M and induced apoptosis in EMT6/AR1 cells, suggesting that benomyl-encapsulated polymeric chitosan-poly(D,L-lactide-co-glycolide) nanoparticles have chemotherapeutic activity against multidrug-resistant cancer cells.

Exoelectrogens Leading to Precise Reduction of Graphene Oxide by Flexibly Switching Their Environment during Respiration.

Reduced graphene oxide (RGO) has been prepared by a simple, cost-effective, and green route. In this work, graphene oxide (GO) has been reduced using Gram-negative facultative anaerobe S. dysenteriae, having exogenic properties of electron transfer via electron shuttling. Apparently, different concentrations of GO were successfully reduced with almost complete mass recovery. An effective role of lipopolysaccharide has been observed while comparing RGO reduced by S. dysenteriae and S. aureus. It was observed that the absence of lipopolysaccharide in Gram-positive S. aureus leads to a disrupted cell wall and that S.aureus could not survive in the presence of GO, leading to poor and inefficient reduction of GO, as shown in our results. However, S. dysenteriae having an outer lipopolysaccharide layer on its cell membrane reduced GO efficiently and the reduction process was extracellular for it. RGO prepared in our work has been characterized by X-ray diffraction, ζ potential, X-ray photoelectron spectroscopy, and Raman spectroscopy techniques, and the results were found to be in good agreement with those of chemically reduced GO. As agglomeration of RGO is the major issue to overcome while chemically reducing GO, we observed that RGO prepared by a bacterial route in our work has ζ potential value of -26.62 mV, good enough to avoid restacking of RGO. The role of exoelectrogens in electron transfer in the extracellular space has been depicted. Toxin released extracellularly during the process paves the way for reduction of GO due to its affinity towards oxygen.

PEGylated FePt-Fe3O4 composite nanoassemblies (CNAs): in vitro hyperthermia, drug delivery and generation of reactive oxygen species (ROS).

Chemothermal therapy is widely used in clinical applications for the treatment of tumors. However, the major challenge is the use of a multifunctional nano platform for significant regression of the tumor. In this study, a simple synthesis of highly aqueous stable, carboxyl enriched, PEGylated mesoporous iron platinum-iron(ii,iii) oxide (FePt-Fe3O4) composite nanoassemblies (CNAs) by a simple hydrothermal approach is reported. CNAs exhibit a high loading capacity ∼90 wt% of the anticancer therapeutic drug, doxorubicin (DOX) because of its porous nature and the availability of abundant negatively charged carboxylic groups on its surface. DOX loaded CNAs (CNAs + DOX) showed a pH responsive drug release in a cell-mimicking environment. Furthermore, the release was enhanced by the application of a alternating current magnetic field. CNAs show no appreciable cytotoxicity in mouse fibroblast (L929) cells but show toxic effects in cervical cancer (HeLa) cells at a concentration of ∼1 mg mL(-1). A suitable composition of CNAs with a concentration of 2 mg mL(-1) can generate a hyperthermic temperature of ∼43 °C. Also, CNAs, because of their Fe and Pt contents, have an ability to generate reactive oxygen species (ROS) in the presence of hydrogen peroxide inside the cancer cells which helps to enhance its therapeutic effects. The synergistic combination of chemotherapy and ROS is very efficient for killing cancer cells.

Polymer Stabilized Fe3O4-Graphene as an Amphiphilic Drug Carrier for Thermo-Chemotherapy of Cancer.

In light of the growing interest in the search for cheap and effective solutions for cancer treatment, we report a simple one pot synthesis of polymer stabilized iron oxide-graphene (PIG) that could be realized on a large scale. The structural (Fe3O4 particle size of ∼11 nm), functional (various oxygen containing moieties), and magnetic (moment of ∼43 emu/g) properties of PIG are explored using various characterization techniques for possible biomedical applications. PIG shows good colloidal stability and is biocompatible even at higher concentrations (2.5 mg/mL) by virtue of cross-linking polymers. The biocompatibility of the composite has been tested using HeLa cell lines by computing the percentage of the reactive oxygen species through the 2,7-dichlorofluorescein (DCF) intensity level. PIG has the ability to load and release both hydrophobic and hydrophilic drugs with a good loading efficiency and capacity. The dug loading efficiency of PIG is measured to be ∼87% and ∼91% for doxorubicin (DOX) and paclitaxel (PTXL), respectively. Under an AC magnetic field, superparamagnetic PIG (2.5 mg/mL) takes less than 16 min to reach the stable hyperthermia temperature, suggesting it as a good anticancer material. A time-dependent cellular uptake of doxorubicin-conjugated PIG has been studied to optimize the parameters for thermo-chemotherapy of cancer. The synergetic effect of both the drug and hyperthermia is observed in the killing of the cancerous cells, verified by computing the cell apoptotic population using a flow cytometer. However, it has been noticed that, even in the absence of chemotherapy, PIG shows good antiproliferative activity with thermotherapy alone.

Effect of HSA coated iron oxide labeling on human umbilical cord derived mesenchymal stem cells.

Human umbilical cord derived mesenchymal stem cells (hUC-MSCs) are known for self-renewal and differentiation into cells of various lineages like bone, cartilage and fat. They have been used in biomedical applications to treat degenerative disorders. However, to exploit the therapeutic potential of stem cells, there is a requirement of sensitive non-invasive imaging techniques which will offer the ability to track transplanted cells, bio-distribution, proliferation and differentiation. In this study, we have analyzed the efficacy of human serum albumin coated iron oxide nanoparticles (HSA-IONPs) on the differentiation of hUC-MSCs. The colloidal stability of the HSA-IONPs was tested over a long period of time (≥20 months) and the optimized concentration of HSA-IONPs for labeling the stem cells was 60 µg ml(-1). Detailed in vitro assays have been performed to ascertain the effect of the nanoparticles (NPs) on stem cells. Lactate dehydrogenase (LDH) assay showed minimum release of LDH depicting the least disruptions in cellular membrane. At the same time, mitochondrial impairment of the cells was also not observed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Flow cytometry analysis revealed lesser generation of reactive oxygen species in HSA-IONPs labeled hUC-MSCs in comparison to bare and commercial IONPs. Transmission electron microscopy showed endocytic engulfment of the NPs by the hUC-MSCs. During the process, the gross morphologies of the actin cytoskeleton were found to be intact as shown by immunofluorescence microscopy. Also, the engulfment of the HSA-IONPs did not show any detrimental effect on the differentiation potential of the stem cells into adipocytes, osteocytes and chondrocytes, thereby confirming that the inherent properties of stem cells were maintained.

Cellular internalization and detailed toxicity analysis of protein-immobilized iron oxide nanoparticles.

Iron oxide nanoparticles (IONPs) have been extensively used for biomedical applications like in the diagnosis and treatment of various diseases, as contrast agents in magnetic resonance imaging, and in targeted drug delivery. Despite several attempts, there is a dearth of information with respect to the cellular response and in-depth toxicity analysis of the nanoparticles. Considering the potential benefits of IONPs, there is a need to study the potential cellular damage associated with IONPs. The size and surface of the particles are some critical factors that should be analyzed when evaluating cytotoxicity. Therefore, in this study, we synthesized and characterized bare (7-9 nm) and protein-coated IONPs of diameter 50-70 nm, and evaluated their toxicity on membrane integrity, intracellular accumulation of reactive oxygen species, and mitochondrial activity in mouse fibroblast cell line by lactate dehydrogenase, 2',7'-dichlorofluorescein diacetate, and [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] (MTT) assays, respectively. Our extensive cytotoxicity analysis demonstrated that the size of the IONPs and their surface coating are the critical determinants of cellular response and potential mechanism toward cytotoxicity. The study of the interactions and assessment of potential toxicity of the nanoparticles with cells/tissues is a key determinant when considering their translation in biomedical applications.

Enhanced specific absorption rate in silanol functionalized Fe3O4 core-shell nanoparticles: study of Fe leaching in Fe3O4 and hyperthermia in L929 and HeLa cells.

Core-shell Fe3O4-SiO2 magnetic nanoparticles (MNPs) have been synthesized using a simple synthesis procedure at different temperatures. These MNPs are used to investigate the effect of surface coating on specific absorption rate (SAR) under alternating magnetic field. The temperature achieved by silica coated Fe3O4 is higher than that by uncoated MNPs (Fe3O4). This can be attributed to extent of increase in Brownian motion for silica coated MNPs. The sample prepared at optimized temperature of 80°C shows the highest SAR value of 111W/g. It is found that SAR value decreases with increase in shell thickness. The chemical stability of these samples is analyzed by leaching experiments at pH 2-7. The silica coated samples are stable up to 7 days even at pH 2. Biocompatibility of the MNPs is evaluated in vitro by assessing their cytotoxicity on L929 and human cervical cancer cells (HeLa cells) using sulforhodamine-B assay. Their hyperthermic killing ability is also evaluated in HeLa cells using the same method. Cells treated with MNPs along with induction heating show decrease in viability as compared to that without induction heating. Further, cell death is found to be ∼55% more in cells treated with silica coated MNPs under induction heating as compared to untreated control. These results establish the efficacy of Fe3O4-SiO2 prepared at 80°C in killing of tumor cells by cellular hyperthermia.

Ce³âº sensitized GdPO4:Tb³âº with iron oxide nanoparticles: a potential biphasic system for cancer theranostics.

We report a biphasic system (BPS) consisting of PEGylated Tb(3+)-doped GdPO4 nanorice sensitized with Ce(3+) (PEG-NRs) and glutamic acid coated iron oxide nanoparticles (IONPs) with multifunctional capabilities. The mesoporous PEG-NRs exhibit green light luminescence properties and a high degree of aqueous stability. Their drug loading and release capacities were investigated for anti-cancer chemo doxorubicin (DOX). Their mesoporous nature and availability of plenty of negatively charged functional groups (-COO(-)) on the surface of PEG-NRs facilitate approximately 94 wt% DOX loading. In vitro studies carried out for PEG-NRs and their biphasic integrated system with iron oxide using HeLa and MCF-7 cell lines demonstrated their cell killing efficacy. The green luminescence observed under confocal laser scanning microscopy (CLSM) confirms the cellular uptake of PEG-NRs by HeLa cell lines and their accumulation in the cytoplasm. Approximately 50-55% of HeLa and MCF-7 cell death was observed after 24 h of incubation with DOX loaded BPS (2 mg IONPs and 0.25 mg PEG-NRs + DOX), which further increased to about 90% when exposed to an AC magnetic field (ACMF) for 25 min. Our findings demonstrate that the therapeutic efficacy of BPS loaded with DOX could be a powerful multimodal system for imaging and synergistic chemo-thermal cancer therapy.

SnO(2) 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.

Combining unique properties of dendrimers and magnetic nanoparticles towards cancer theranostics.

Magnetic nanoparticles (MNPs) are a well explored class of nanomaterials, known for their high magnetization and biocompatibility thus finding their way in several biomedical applications viz., drug delivery, magnetic resonance imaging contrast agent, immunoassay, detoxification of biological fluids and cell separation, biosensing and hyperthermia. On other hand, dendrimers are a class of hyperbranched, mostly symmetrical polymers that originate from a central core with repetitive branching units, called monomers, thus forming a globular structure. Due to their structural properties and controlled size, dendrimers have emerged as an attractive material for biomedical applications particularly as carriers for therapeutic cargo. Of late, researchers have started attempting to combine the unique features of dendrimer chemistry with the versatile magnetic nanoparticles to provide a facile platform for enhanced therapeutics and biomedical applications. This review intends to present the advances made towards fabrication of dendrimer based magnetic nanoparticles with varied surface architecture and their contribution towards theranostics, particularly for cancer.