Microwave Responsive Nanoplatform via P-Selectin Mediated Drug Delivery for Treatment of Hepatocellular Carcinoma with Distant Metastasis.

Hepatocellular carcinoma (HCC) with metastatic disease is associated with a low survival in clinical practice. Many curative options including liver resection, transplantation, and thermal ablation are effective in local but limited for patients with distant metastasis. In this study, the efficacy, specificity, and safety of P-selectin targeted delivery and microwave (MW) responsive drug release is investigated for development of HCC therapy. By encapsulating doxorubicin (DOX) and MW sensitizer (1-butyl-3-methylimidazolium-l-lactate, BML) into fucoidan conjugated liposomal nanoparticles (TBP@DOX), specific accumulation and prominent release of DOX in orthotopic HCC and lung metastasis are achieved with adjuvant MW exposure. This results in orthotopic HCC growth inhibition that is not only 1.95-fold higher than found for nontargeted BP@DOX and 1.6-fold higher than nonstimuli responsive TP@DOX but is also equivalent to treatment with free DOX at a 10-fold higher dose. Furthermore, the optimum anticancer efficacy against distant lung metastasis and effective prevention of widespread dissemination with a prolonged survival is described. In addition, no adverse metabolic events are identified using the TBP@DOX nanodelivery system despite these events being commonly observed with traditional DOX chemotherapy. Therefore, administering TBP@DOX with MW exposure could potentially enhance the therapeutic efficacy of thermal-chemotherapy of HCC, especially those in the advanced stages.

A novel platform for enhanced biosensing based on the synergy effects of electrospun polymer nanofibers and graphene oxides.

A novel biosensing platform was developed by combining the advantages of electrospun poly(vinyl alcohol) (PVA)/chitosan nanofibers and graphene oxides (GO). Glucose oxidase (GOD) was employed as a model enzyme. By co-electrospinning the solution of PVA, chitosan, GOD and GO, the PVA/chitosan/GOD/GO nanofibers were directly modified on the platinum (Pt) electrode. The UV-vis spectra and the FTIR spectra were used to characterize the GO nanosheets. The morphologies of fabricated electrospun nanofibers were characterized by high resolution scanning electron microscopy. After a thin layer of nafion was modified on the surface of matrix, the as-prepared electrode was used to detect glucose. The electrode exhibited great advantages in high sensitivity, low detection limit and wide linear range. In the meantime, the electrode showed good stability, acceptable reproducibility, and excellent anti-interference capability for ascorbic acid, uric acid, lactose and sucrose. Moreover, the novel biosensor was successfully applied for the glucose determination in human serum samples. The mechanism of efficient biosensing of the nafion/PVA/chitosan/GOD/GO/Pt electrode was analyzed in detail and the results show that it can be due to the synergy effects of electrospun nanofibers and GO nanosheets.

A study of the electron transfer and photothermal effect of gold nanorods on a glucose biosensor.

A new glucose biosensor based on the electron transfer and photothermal effect of gold nanorods (GNRs) is reported here. The biosensor was prepared by immobilizing glucose oxidase (GOx) on a platinum (Pt) electrode by a composite film consisting of GNRs, polyvinyl butyral (PVB) and glutaraldehyde. GNRs were synthesized by a gold seed-mediated cetyltrimethylammonium bromide (CTAB) surfactant-assisted approach. The fabrication, characterization and analytical performance of the glucose biosensor based on GNRs are described in this paper. Moreover, the modulation of the biosensor by the photothermal effect based on the unique surface plasma resonance (SPR) property of GNRs was investigated for the first time. The results show that the current response of a glucose biosensor can significantly increase, induced by the electrical conductivity and photothermal effect of GNRs.

l-Cysteine decorated nanoscale metal-organic frameworks delivering valproic acid/cisplatin for drug-resistant lung cancer therapy.

We design multifunctional CDDP-VPA@ZrMOF-Cys-PEG nanoparticles (CVZP NPs) based on the properties of valproic acid (VPA) that can downregulate the expression of vascular endothelial growth factor (VEGF) to reduce the drug resistance of tumor cells. In vivo experiments confirm that chemotherapy combined with microwave thermal therapy (MWTT) can significantly improve the therapeutic effect of cisplatin-resistant lung cancer.

High Biocompatible ZIF-8 Coated by ZrO2 for Chemo-microwave Thermal Tumor Synergistic Therapy.

The zeolitic imidazolate framework-8 (ZIF-8) is a specifically promising drug carrier due to its excellent intrinsic properties. However, the high toxicity of ZIF-8 nanoparticles severely limits their further research and clinical application. In this work, the biocompatibility of ZIF-8 nanoparticles is greatly improved by coating ZrO2 onto the surface. The survival rate of cells and mice in the ZIF-8@ZrO2 nanocomposite group is significantly increased compared with the undecorated ZIF-8 nanoparticle group. Doxorubicin (DOX) as a chemotherapeutic drug is deposited during the ZIF-8 growth by a facile one-pot method. Ionic liquid (IL) is loaded into the pore of the ZIF-8/DOX@ZrO2 nanocomposites for enhancing microwave thermal therapy. The tumor inhibition rate of ZIF-8/DOX@ZrO2@IL nanocomposites with synergistic microwave thermal therapy and chemotherapy is obviously higher than in other groups. In addition, the ZIF-8/DOX@ZrO2@IL nanocomposites are used for real-time monitoring of the therapeutic outcomes due to the excellent computed tomography contrast agent, ZrO2. Therefore, such a ZrO2 coating strategy shows great promise for overcoming high toxicity of ZIF-8 nanoparticles, which offers a new platform for tumor synergistic microwave thermal therapy and chemotherapy using the ZIF-8/DOX@ZrO2@IL nanocomposite as a theranostic nanocarrier.

Interlayer expansion of 2D MoS2 nanosheets for highly improved photothermal therapy of tumors in vitro and in vivo.

Interlayer-expanded MoS2 (E-MoS2) nanosheets with an interlayer spacing of 0.94 nm are demonstrated to show an high photothermal conversion efficiency of ∼62%. More importantly, such biocompatible E-MoS2 nanosheets show highly improved photothermal therapy (PTT) of tumors in vitro and in vivo under near-infrared light irradiation.

Biocompatible and biodegradable zeolitic imidazolate framework/polydopamine nanocarriers for dual stimulus triggered tumor thermo-chemotherapy.

Zeolitic imidazolate frameworks (ZIFs) have attracted great interest as pH-sensitive drug carrier because of high drug loading and intrinsic biodegradability. In this work, a biocompatible NIR and pH-responsive drug delivery nanoplatform based on ZIFs (PDA-PCM@ZIF-8/DOX) is synthesized for in vivo cancer therapy. The biocompatibility of ZIFs is greatly improved by polydopamine (PDA) modifying and proved by cytotoxicity and in vivo acute toxicity evaluation. The degradability is also regulated in an appropriate rate. Due to mild reaction condition of ZIFs, the synthesis and drug loading is achieved in one pot with high loading (37.86%) and encapsulation rate (78.76%). Meanwhile, PDA acts as a photothermal transfer agent to trigger thermal response switch of phase change materials for NIR controlled drug release. Under the dual stimulus of NIR and acid environment, the drug release is as high as 78%, while only 21% is released without stimulus, showing a remarkable effect of control release. In vivo anti-tumor experiments demonstrate the high tumor inhibition rate of photothermal-chemotherapy group with a significant synergistic effect. The biocompatible and biodegradable drug delivery platform based on ZIFs has shown great promise for future clinic cancer therapy.

Mitochondria-targeted zirconium metal-organic frameworks for enhancing the efficacy of microwave thermal therapy against tumors.

Although microwave (MW) thermal therapy has been widely studied for the treatment of tumors due to its less invasiveness, recurrence of tumors is still observed because of the relatively low bioavailability of MW sensitizers. For enhancing the bioavailability of MW sensitizers, triphenyl phosphate (TPP)-conjugated and doxorubicin (DOX)-loaded porous zirconium metal-organic framework nanocubes (ZrMOF NCs) modified with polyethylene glycol (PEG), ZrMOF-PEG-TPP@DOX NCs, were prepared as a MW sensitizer with mitochondrial-targeting ability. Moreover, the mitochondria are more susceptible to heat than the tumor tissues; this leads to improved tumor cell apoptosis. The results of this study indicate that ZrMOF NCs exhibit excellent heating effects due to the increased collisions of ions in the micropores of ZrMOFs under MW irradiation. In addition, ZrMOF-PEG-TPP@DOX NCs show preferential aggregation in the mitochondria, confirmed by confocal microscopy images. In vivo MW thermal therapeutic efficacy of ZrMOF-PEG-TPP@DOX NCs + MW is also better without recurrence during treatment than that of ZrMOF-PEG@DOX NCs + MW at a similar thermal therapeutic temperature; this reveals that the mitochondrial-targeting strategy can enhance the MW thermal therapeutic efficacy. This study provides a new biosafe MW sensitizer with mitochondrial-targeting ability for enhancing the efficacy of MW thermal therapy against tumors.

Imaging-guided synergetic therapy of orthotopic transplantation tumor by superselectively arterial administration of microwave-induced microcapsules.

It is an ambitious target to improve overall Hepatocellular Carcinoma therapeutic effects. Recently, MW ablation has emerged as a powerful thermal ablation technique, affording favorable survival with excellent local tumor control. To achieve better therapeutic effects of MW ablation, MW sensitizers are prepared for enhanced MW ablation to preferentially heat tumor territory. However, it is still not practicable for treatment of the orthotopic transplantation tumor. Herein, biocompatible and degradable methoxy poly(ethylene glycol)-poly(lactic-co-glycolic acid) (mPEG-PLGA) microcapsules with hierarchical structure have been designed for microwave-induced tumor therapy. Chemical drug doxorubicin hydrochloride (DOX·HCl), microwave (MW) sensitizers and CT imaging contrast MoS2 nanosheets and MR imaging contrast Fe3O4 nanoparticles are co-incorporated into the microcapsules. In vitro/vivo MR/CT dual-modal imaging results prove the potential application for guiding synergetic therapy and predicting post-therapy tumor progression in the orthotopic transplantation tumor model. After blocking the tumor-feeding arteries, these microcapsules not only exclude the cooling effect by cutting off the blood flow but also enhance MW heating conversion at tumor site. The focused MW heating makes microcapsules mollescent or ruptured and releases DOX·HCl from the microcapsules, achieving the controlled release of drugs for chemical therapy. Compared with MW ablation, 29.4% increase of necrosis diameter of normal liver in rabbit is obtained under MW ablation combined with transcatheter arterial blocking, and the average size of necrosis and inhibition rate of VX-2 liver orthotopic transplantation tumor in rabbit has increased by 129.33% and 73.46%. Moreover, it is proved that the superselectively arterial administration of the as-prepared microcapsules has no recognizable toxicity on the animals. Therefore, this research provides a novel strategy for the construction of MW-induced microcapsules for orthotopic transplantation tumor ablation with the properties of MW sensitizing, superselective arterial blocking, control release and enhanced accumulation of DOX·HCl, and MR/CT dual-modal imaging, which exhibits great potential applications in the field of HCC therapy.

Biocompatible Hollow Polydopamine Nanoparticles Loaded Ionic Liquid Enhanced Tumor Microwave Thermal Ablation in Vivo.

Tumor microwave thermal therapy (MWTT) has attracted more attention because of the minimal damage to body function, convenient manipulation and low complications. Herein, a novel polydopamine (PDA) nanoparticle loading ionic liquids (ILs/PDA) as microwave susceptible agent is introduced for enhancing the selectivity and targeting of MWTT. ILs/PDA nanocomposites have an excellent microwave heating efficiency under an ultralow microwave power irradiation. Encouraging antitumor effect was observed when tumor bearing mice received ILs/PDA nanoparticles by intravenous injection and only single microwave irradiation. PDA nanoparticles with gold nanoparticles in core were constructed for tumor targeting study by ICP-MS and about 15% PDA nanoparticles were founded in tumor. Furthermore, the cytotoxicity and acute toxicity study in vivo of PDA showed the excellent biocompatibility of ILs/PDA nanocomposites. In addition, the degradation of ILs/PDA nanocomposites in simulated body fluid illustrated the low potential hazard when they entered the blood. The emergence of PDA as a novel and feasible platform for cancer thermal therapy will promote the rapid development of microwave therapy in clinics.

Using silver nanoparticle to enhance current response of biosensor.

In this paper, we present a simple procedure to increase the sensitivity of a glucose biosensor. The feasibility of an amperometric glucose biosensor based on immobilization of glucose oxidase (GOx) in silver (Ag) sol was investigated for the first time. GOx was simply mixed with Ag nanoparticles and cross-linked with a polyvinyl butyral (PVB) medium by glutaraldehyde. Then a platinum electrode was coated with the mixed solution. The effects of the amount of the Ag particles used, with respect to the current response for enzyme electrodes, were studied. A set of experimental results indicate that the current response for the enzyme electrode containing hydrophobic Ag sol increased from 0.531 to 31.17 microA in the solution of 10 mmol/L beta-D glucose. The time reaching the steady-state current response reduced from 60 to 20s, three times less than those without Ag particles involved.

One-pot synthesis of active copper-containing carbon dots with laccase-like activities.

Herein, an effective strategy for designing a new type of nanozyme, blue fluorescent laccase mimics, is reported. Active copper-containing carbon dots (Cu-CDs) were synthesized through a simple, nontoxic and one-pot hydrothermal method, which showed favorable photoluminescence properties and good photostability under high-salt conditions or in a broad pH range (3.0-13.5). The Cu-CDs possessed intrinsic laccase-like activities and could catalyze the oxidation of the laccase substrate p-phenylenediamine (PPD) to produce a typical color change from colorless to brown. Poly(methacrylic acid sodium salt) (PMAA) not only was used as the carbon source and reducing agent, but also provided carboxyl groups to assist flocculation between Cu-CDs and polyacrylamide, which facilitated the removal of PPD. Importantly, the intrinsic fluorescence of the as-prepared Cu-CDs could indicate the presence of hydroquinone, one of the substrates of laccases, based on laccase mimics and fluorescence quenching.

Fluorescence switching method for cascade detection of salicylaldehyde and zinc(II) ion using protein protected gold nanoclusters.

A new fluorescence switching sensor for cascade detection of salicylaldehyde (SA) and Zinc(II) ion was developed based on bovine serum albumin protected gold nanoclusters (BSA-AuNCs). In the detection, SA interacted with amino groups of BSA-AuNCs, inducing simultaneous formation of fluorescent Schiff base and fluorescence quenching of AuNCs. Zn(II) could further strongly coordinate with the Schiff base ligands, leading to blue-shift and increase of the fluorescence from Schiff base-metal coordination complexes and simultaneous recovery of fluorescence from AuNCs. The new fluorescence switching sensor for Zn(2+) detection has advantages of simplicity, rapidity, naked-eye detection, high sensitivity and selectivity. The linear range of the method for Zn(2+) detection is from 0.1 µM to 100 µM with the limit of detection (LOD) of 29.28 nM. In practical samples, the recoveries of the samples ranged from 99.63% to 100.58%.

Gelatin microcapsules for enhanced microwave tumor hyperthermia.

Local and rapid heating by microwave (MW) irradiation is important in the clinical treatment of tumors using hyperthermia. We report here a new thermo-seed technique for the highly efficient MW irradiation ablation of tumors in vivo based on gelatin microcapsules. We achieved 100% tumor elimination in a mouse model at an ultralow power of 1.8 W without any side-effects. The results of MTT assays, a hemolysis test and the histological staining of organs indicated that the gelatin microcapsules showed excellent compatibility with the physiological environment. A possible mechanism is proposed for MW hyperthermia using gelatin microcapsules. We also used gelatin microcapsules capped with CdTe quantum dots for in vivo optical imaging. Our study suggests that these microcapsules may have potential applications in imaging-guided cancer treatment.

A new amperometric glucose biosensor based on one-step electrospun poly(vinyl alcohol)/chitosan nanofibers.

In this work, a new glucose amperometric biosensor was developed by directly electrospinning poly(vinyl alcohol)/chitostan nanofibers on the surface of the platinum electrode, in which glucose oxidase (GOD) was effectively immobilized in nanofibers by encapsulation. After been cross-linked in glutaraldehyde vapor and modified with a thin nafion film, the nanofibers (PVA/chitosan/GOD)/nafion electrode was used for glucose amperometric measurements. The electrospun nanofibrous enzyme membrane served as a better sensing element than the casing one due to the unique properties of nanofibers such as the special three-dimensional network structure, large pores, high porosity, and large surface to volume ratios. The as-prepared biosensor showed a wide linear calibration range, low detection limit, and low apparent Michaelis-Menten constant in the glucose determination. The stability, reproducibility and anti-interference capability of biosensor were also presented. Furthermore, the new biosensor was successfully applied to detect glucose in human serum samples.

Highly H2O2-sensitive electrospun quantum dots nanocomposite films for fluorescent biosensor.

Bright CdSe quantum dots (QDs)/polycaprolactone (PCL) nanocomposite fluorescent films were fabricated by electronspinning. By using chloroform and N,N-dimethylformamide as electronspinning solvent, the oil-soluble CdSe QDs were uniformly distributed in PCL fibers, and were directly employed as optical probe without any modification processing. The fluorescences of CdSe QDs/PCL nanocomposite films were quickly quenched when the films were contacted with H2O2, solution. In the presence of glucose oxidase (GOD), the fluorescence intensities of these fluorescent films exhibit a liner change with the concentrations of glucose. The H2O2-sensitive electrospun QDs nanocomposite films are highly uniform and repeatable, demonstrating the potential to fabricate stable, sensitive and recyclable fluorescent biosensor for the detection different H2O2-generating oxidases and their substrates.

Synthesis of fluorescent Ag nanoclusters and their application in α-L-fucosidase detection.

Highly fluorescent Ag nanoclusters (NCs) were successfully prepared by a simple and nontoxic approach, and the as-prepared Ag NCs could be utilized for the AFu detection with a lower detection limit of 0.001 U L(-1).

A practical glucose biosensor based on Fe(3)O(4) nanoparticles and chitosan/nafion composite film.

A practical glucose biosensor was developed by combining the intrinsic peroxidase-like activity of Fe(3)O(4) nanoparticles (Fe(3)O(4) NPs) and the anti-interference ability of the nafion film. Glucose oxidase (GOD) was simply mixed with Fe(3)O(4) NPs and cross-linked on the Pt electrode with chitosan (Cs) medium by glutaraldehyde, and then covered with a thin nafion film. The biosensor showed high sensitivity (11.54 microAcm(-2)mM(-1)), low detection limit (6 x10(-6)M), and good storage stability. A linear calibration plot was obtained in the wide concentration range from 6 x10(-6) to 2.2 x10(-3)M. The modified electrode could virtually eliminate the interference during the detection of glucose. Furthermore, the biosensor was successfully applied to detect glucose in human serum sample. This fabrication of glucose biosensor was of considerable interest due to its promise for simple procedure and optimizing conditions in practical application.

Amperometric glucose biosensor based on a gold nanorods/cellulose acetate composite film as immobilization matrix.

We report on the utilization of gold nanorods to create a highly responsive glucose biosensor. The feasibility of an amperometric glucose biosensor based on immobilization of glucose oxidase (GOx) in gold nanorod is investigated. GOx is simply mixed with gold nanorods and cross-linked with a cellulose acetate (CA) medium by glutaraldehyde. The adsorption of GOx on the gold nanorods is confirmed by X-ray photoelectron spectroscopy (XPS) measurements. Circular dichroism (CD) and UV-spectrum results show that the activity of GOx was preserved after conjugating with gold nanorods. The current response of modified electrode is 10 times higher than that of without gold nanorods. Under optimal conditions, the biosensor shows high sensitivity (8.4 microA cm(-2) mM(-1)), low detection limit (2x10(-5) M), good storage stability and high affinity to glucose (K(m)(app)=3.84 mM). A linear calibration plot is obtained in the wide concentration range from 3x10(-5) to 2.2x10(-3) M.