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.

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.

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.

Dual pH and temperature stimuli-responsive magnetic nanohydrogels for thermo-chemotherapy.

Dual stimuli pH and temperature-responsive nanohydrogels based on poly(N-isopropylacrylamide)-chitosan have been synthesized. Fe3O4 magnetic nanoparticles (NPs) (-12 nm) have been incorporated into hydrogels to achieve temperature optimized magnetic nanohydrogel (MNHG) for magnetic hyperthermia with lower critical solution temperature, LCST > 42 degrees C. The composite was further investigated for its potential application in drug delivery and in vitro cancer cell cytotoxicity. Water-bath assisted drug release studies were carried out using anti-cancer drug doxorubicin (DOX) in acetate buffer medium (pH - 4.6) to mimic tumor cell environment which is slightly acidic in nature. The pH and temperature responsiveness of the system was demonstrated by DOX release under different conditions. The released amount of DOX was found to be nearly 4 microg/mg above hyperthermia temperature (-42 degrees C) as opposed to only 1.9 microg/mg of MNHG at physiological temperature (37 degrees C) under acidic environment (pH - 4.6). Further, AC magnetic field (AMF) induced heating of NPs entrapped inside hydrogels showed appreciable reduction of cell population in human breast (MCF-7) and cervical carcinoma (HeLa) cell lines for given duration of field exposures. Quantitatively, death percentages of HeLa cells were nearly 35 and 45% while for MCF-7, these were 20 and 70% when exposed to AMF for 10 and 30 min, respectively. Further the cell killing efficacy of MNHG loaded with DOX was assessed under AMF using HeLa cell lines. The AMF induced heat triggered DOX release from the MNHG which enhances the cell death up to 85% due to combined effect of thermo-chemotherapeutics. The present system with both pH and temperature responsivity serves as a promising candidate for a combination therapy.

Fabrication of a glucose biosensor based on citric acid assisted cobalt ferrite magnetic nanoparticles.

A novel and practical glucose biosensor was fabricated with immobilization of Glucose oxidase (GOx) enzyme on the surface of citric acid (CA) assisted cobalt ferrite (CF) magnetic nanoparticles (MNPs). This innovative sensor was constructed with glassy carbon electrode which is represented as (GOx)/CA-CF/(GCE). An explicit high negative zeta potential value (-22.4 mV at pH 7.0) was observed on the surface of CA-CF MNPs. Our sensor works on the principle of detection of H2O2 which is produced by the enzymatic oxidation of glucose to gluconic acid. This sensor has tremendous potential for application in glucose biosensing due to the higher sensitivity 2.5 microA/cm2-mM and substantial increment of the anodic peak current from 0.2 microA to 10.5 microA.

Wet-chemical green synthesis of L-lysine amino acid stabilized biocompatible iron-oxide magnetic nanoparticles.

In this paper, we report a novel method for the synthesis of L-Lysine (lys) amino acid coated maghemite (gamma-Fe2O3) magnetic nanoparticles (MNPs). The facile and cost effective method permitted preparation of the high-quality superparamagnetic gamma-Fe2O3 MNPs with hydrophilic and biocompatible nature. For this work, first we synthesized magnetite phase Fe3O4/lys by wet chemical method and oxidized to y-Fe2O3 in controlled oxidizing environment, as evidenced by XRD and VSM magnetometry. The crystallite size and magnetization of gamma-Fe2O3/lys MNPs was found to be 14.5 nm, 40.6 emu/gm respectively. The surface functionalization by L-lysine amino acid and metal-ligand bonding was also confirmed by FTIR spectroscopy. The hydrodynamic diameter, colloidal stability and surface charge on MNPs were characterized by DLS and zeta potential analyser.

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.

Synthesis of hydrophilic superparamagnetic magnetite nanoparticles via thermal decomposition of Fe(acac), in 80 vol% TREG + 20 vol% TREM.

In this paper, we report single step synthesis of hydrophilic superparamagnetic magnetite nanoparticles by thermolysis of Fe(acac)3 and their characterization of the properties relevant to biomedical applications like hyperthermia and magnetic resonance imaging (MRI). Size and morphology of the particles were determined by Transmission electron microscopy (TEM) while phase purity and structure of the particles were identified by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Magnetic properties were evaluated using vibrating sample magnetometer (VSM) and superconducting quantum interference device (SQUID) measurements. The as prepared nanoparticles were found to be superparamagnetic with the blocking temperature of 136 K and were easily suspendable in water. Cytotoxicity studies on human cervical (SiHa), mouse melanoma (B16F10) and mouse primary fibroblast cells demonstrated that up to a dose of 0.1 mg/ml, the magnetite nanoparticles were nontoxic to the cells. To evaluate the feasibility of their uses in hyperthermia and MRI applications, specific absorption rate (SAR) and spin-spin relaxation time (T2) were measured respectively. SAR has been calculated to be above 80 Watt/g for samples with the iron concentration of 5-20 mg/ml at 10 kA/m AC magnetic field and 425 kHz frequency. r2 relaxivity value was measured as 358.4 mM(-1)S(-1) which is almost double as compared to that of the Resovist, a commercially available MRI contrast agent. Thus the as-prepared magnetite nanoparticles may be used for hyperthermia and MRI applications due to their promising SAR and r2 values.

Nanoscale assembly of amine functionalized colloidal iron oxide.

We demonstrate a single-step facile approach for highly water stable assembly of amine-functionalized Fe(3)O(4) nanoparticles using thermal decomposition of Fe-chloride precursors in ethylene glycol medium in the presence of ethylenediamine. The average size of nanoassemblies is 40±1 nm, wherein the individual nanoparticles are about 6 nm. Amine functionalized properties are evident from FTIR, thermal and elemental analysis. The saturation magnetization and spin-echo r(2) of the nanoassemblies were measured to be 64.3 emu/g and 314.6 mM(-1)s(-1), respectively. The higher value of relaxivity ratio (r(2)/r(1)=143) indicates that nanoassemblies are a promising high efficiency T2 contrast agent platform.

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.

Magnetic nanoparticle-polyelectrolyte interaction: a layered approach for biomedical applications.

This study describes the surface modification of magnetic nanoparticles using two different approaches. The first approach consists of an in situ modification of the surface during the precipitation of the magnetic nanoparticles while the second approach consists of a post-modification of the surface after the formation of the magnetic nanoparticles. In the latter case, we adopted the Layer-by-Layer assembly of polyelectrolyte multilayers of poly(diallyl-dimethylammonium) chloride and poly(styrenesulfonate) to build a polymeric shell around the magnetic nanoparticle core, thereby intentionally conferring to this hybrid core-shell the same charge as the charge of the polyelectrolyte deposited in the last layer. Electrophoretic measurements reveal charge reversal indicating successful Layer-by-Layer deposition while magnetization studies show that the superparamagnetic behavior is not much affected by the presence of polyelectrolytes on the modified magnetic nanoparticles. Fourier transform infrared and thermogravimetry analysis results underline that the various polyelectrolytes employed, in both the methodologies adopted, were successfully bound to the nanoparticles.

Comparative evaluation of heating ability and biocompatibility of different ferrite-based magnetic fluids for hyperthermia application.

In this study, lauric acid-coated, superparamagnetic, nanoparticle-based magnetic fluids of different ferrites (Fe(3)O(4), MnFe(2)O(4), and CoFe(2)O(4)) were prepared and compared in terms of heating ability and biocompatibility to evaluate the feasibility of use in hyperthermia treatment of cancer. All the magnetic fluids prepared had particles of average sizes 9-11 nm. Heating ability of these magnetic fluids was evaluated by calorimetric measurement of specific absorption rate (SAR) at 300 kHz frequency and 15 kA/m field. Fe(3)O(4) and MnFe(2)O(4) showed higher SAR (120 and 97 W/g of ferrite, respectively) than CoFe(2)O(4) (37 W/g of ferrite). In vitro study on BHK 21 cell lines showed dose-dependent cell viability for all the magnetic fluids. Threshold-biocompatible ferrite concentration for all the magnetic fluids was 0.1 mg/mL. Above 0.2 mg/mL, CoFe(2)O(4) was more toxic than the other magnetic fluids. On intravenous injection of different doses (50, 200, and 400 mg/kg body weight) of magnetic fluids in mice, no significant changes in hematological and biochemical parameters were observed for Fe(3)O(4) and MnFe(2)O(4). With CoFe(2)O(4), an increase in SGPT levels at a dose rate of 400 mg/kg body weight was observed, indicating its mild hepatotoxic effect. However, histology of different vital organs showed no pathological changes for all the three magnetic fluids. Further, long term in vivo evaluation of biocompatibility of the lauric acid-coated ferrites is warranted. This study shows that lauric acid-coated, superparamagnetic Fe(3)O(4) and MnFe(2)O(4) may be used for hyperthermia treatment and are to be preferred over CoFe(2)O(4).

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.

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.

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.

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.

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.

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.

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.