Magnetic-composite-modified polycrystalline silicon nanowire field-effect transistor for vascular endothelial growth factor detection and cancer diagnosis.

This study proposes a vascular endothelial growth factor (VEGF) biosensor for diagnosing various stages of cervical carcinoma. In addition, VEGF concentrations at various stages of cancer therapy are determined and compared to data obtained by computed tomography (CT) and cancer antigen 125 (CA-125). The increase in VEGF concentrations during operations offers useful insight into dosage timing during cancer therapy. This biosensor uses Avastin as the biorecognition element for the potential cancer biomarker VEGF and is based on a n-type polycrystalline silicon nanowire field-effect transistor (poly-SiNW-FET). Magnetic nanoparticles with poly[aniline-co-N-(1-one-butyric acid) aniline]-Fe3O4 (SPAnH-Fe3O4) shell-core structures are used as carriers for Avastin loading and provide rapid purification due to their magnetic properties, which prevent the loss of bioactivity; furthermore, the high surface area of these structures increases the quantity of Avastin immobilized. Average concentrations in human blood for species that interfere with detection specificity are also evaluated. The detection range of the biosensor for serum samples covers the results expected from both healthy individuals and cancer patients.

Magnetic resonance monitoring of focused ultrasound/magnetic nanoparticle targeting delivery of therapeutic agents to the brain.

The superparamagnetic properties of magnetic nanoparticles (MNPs) allow them to be guided by an externally positioned magnet and also provide contrast for MRI. However, their therapeutic use in treating CNS pathologies in vivo is limited by insufficient local accumulation and retention resulting from their inability to traverse biological barriers. The combined use of focused ultrasound and magnetic targeting synergistically delivers therapeutic MNPs across the blood-brain barrier to enter the brain both passively and actively. Therapeutic MNPs were characterized and evaluated both in vitro and in vivo, and MRI was used to monitor and quantify their distribution in vivo. The technique could be used in normal brains or in those with tumors, and significantly increased the deposition of therapeutic MNPs in brains with intact or compromised blood-brain barriers. Synergistic targeting and image monitoring are powerful techniques for the delivery of macromolecular chemotherapeutic agents into the CNS under the guidance of MRI.

Enhanced therapeutic agent delivery through magnetic resonance imaging-monitored focused ultrasound blood-brain barrier disruption for brain tumor treatment: an overview of the current preclinical status.

Malignant glioma is a severe primary CNS cancer with a high recurrence and mortality rate. The current strategy of surgical debulking combined with radiation therapy or chemotherapy does not provide good prognosis, tumor progression control, or improved patient survival. The blood-brain barrier (BBB) acts as a major obstacle to chemotherapeutic treatment of brain tumors by severely restricting drug delivery into the brain. Because of their high toxicity, chemotherapeutic drugs cannot be administered at sufficient concentrations by conventional delivery methods to significantly improve long-term survival of patients with brain tumors. Temporal disruption of the BBB by microbubble-enhanced focused ultrasound (FUS) exposure can increase CNS-blood permeability, providing a promising new direction to increase the concentration of therapeutic agents in the brain tumor and improve disease control. Under the guidance and monitoring of MR imaging, a brain drug-delivery platform can be developed to control and monitor therapeutic agent distribution and kinetics. The success of FUS BBB disruption in delivering a variety of therapeutic molecules into brain tumors has recently been demonstrated in an animal model. In this paper the authors review a number of critical studies that have demonstrated successful outcomes, including enhancement of the delivery of traditional clinically used chemotherapeutic agents or application of novel nanocarrier designs for actively transporting drugs or extending drug half-lives to significantly improve treatment efficacy in preclinical animal models.

Inhibitory effects of 1,2,3,4,6-penta-O-galloyl-beta-D-glucopyranose on biofilm formation by Staphylococcus aureus.

1,2,3,4,6-Penta-O-galloyl-ß-D-glucopyranose (PGG) is an active ingredient in plants that are commonly used in Chinese medicine to treat inflammation. We demonstrate here that PGG, at 6.25 µM, does not inhibit the growth of Staphylococcus aureus, and yet it prevents biofilm formation on polystyrene and polycarbonate surfaces. At the same concentration, PGG is not toxic to human epithelial and fibroblast cells. PGG has an IB50 value, i.e., the PGG concentration that inhibits 50% biofilm formation, of 3.6 µM. The value is substantially lower than that of N-acetylcysteine, iodoacetamide, and N-phenyl maleimide, which are known to inhibit biofilm formation by S. aureus. Biochemical and scanning electron microscopy results also reveal that PGG inhibits initial attachment of the bacteria to solid surface and the synthesis of polysaccharide intercellular adhesin, explaining how PGG inhibits biofilm formation. The results of this study demonstrate that coating PGG on polystyrene and silicon rubber surfaces with polyaniline prevents biofilm formation, indicating that PGG is highly promising for clinical use in preventing biofilm formation by S. aureus.

In vivo MR quantification of superparamagnetic iron oxide nanoparticle leakage during low-frequency-ultrasound-induced blood-brain barrier opening in swine.

PURPOSE: To verify that low-frequency planar ultrasound can be used to disrupt the BBB in large animals, and the usefulness of MRI to quantitatively monitor the delivery of superparamagnetic iron oxide (SPIO) nanoparticles into the disrupted regions. MATERIALS AND METHODS: Two groups of swine subjected to craniotomy were sonicated with burst lengths of 30 or 100 ms, and one group of experiment was also performed to confirm the ability of 28-kHz sonication to open the BBB transcranially. SPIO nanoparticles were administered to the animals after BBB disruption. Procedures were monitored by MRI; SPIO concentrations were estimated by relaxivity mapping. RESULTS: Sonication for 30 ms created shallow disruptions near the probe tip; 100-ms sonications after craniotomy can create larger and more penetrating openings, increasing SPIO leakage ∼3.6-fold than 30-ms sonications. However, this was accompanied by off-target effects possibly caused by ultrasonic wave reflection. SPIO concentrations estimated from transverse relaxation rate maps correlated well with direct measurements of SPIO concentration by optical emission spectrometry. We have also shown that transcranial low-frequency 28-kHz sonication can induce secure BBB opening from longitudinal MR image follow up to 7 days. CONCLUSION: This study provides valuable information regarding the use low-frequency ultrasound for BBB disruption and suggest that SPIO nanoparticles has the potential to serve as a thernostic agent in MRI-guided ultrasound-enhanced brain drug delivery.

Preparation of a porous composite film for the fabrication of a hydrogen peroxide sensor.

A series of dopant-type polyaniline-polyacrylic acid composite (PAn-PAA) films with porous structures were prepared and developed for an enzyme-free hydrogen peroxide (H(2)O(2)) sensor. The composite films were highly electroactive in a neutral environment as compared to polyaniline (PAn). In addition, the carboxyl group of the PAA was found to react with H(2)O(2) to form peroxy acid groups, and the peroxy acid could further oxidize the imine structure of PAn to form N-oxides. The N-oxides reverted to their original form via electrochemical reduction and increased the reduction current. Based on this result, PAn-PAA was used to modify a gold electrode (PAn-PAA/Au) as a working electrode for the non-enzymatic detection of H(2)O(2). The characteristics of the proposed sensors could be tuned by the PAA/PAn molar ratio. Blending PAA with PAn enhanced the surface area, electrocatalytic activity, and conductivity of these sensors. Under optimal conditions, the linear concentration range of the H(2)O(2) sensor was 0.04 to 12 mM with a sensitivity of 417.5 µA/mM-cm(2). This enzyme-free H(2)O(2) sensor also exhibited a rapid response time, excellent stability, and high selectivity.

Blood-brain barrier disruption with focused ultrasound enhances delivery of chemotherapeutic drugs for glioblastoma treatment.

PURPOSE: To demonstrate the feasibility of using focused ultrasound to enhance delivery of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) to glioblastomas in rats with induced tumors and determine if such an approach increases treatment efficacy. MATERIALS AND METHODS: All animal experiments were approved by the animal committee and adhered to the experimental animal care guidelines. A 400-kHz focused ultrasound generator was used to transcranially disrupt the blood-brain barrier (BBB) in rat brains by delivering burst-tone ultrasound energy in the presence of microbubbles. The process was monitored in vivo by using magnetic resonance (MR) imaging. Cultured C6 glioma cells implanted in Sprague-Dawley rats were used as the tumor model. BCNU (13.5 mg/kg) was administered intravenously and its concentration in brains was quantified by using high-performance liquid chromatography. MR imaging was used to evaluate the effect of treatments longitudinally, including analysis of tumor progression and animal survival, and brain tissues were histologically examined. Methods including the two-tailed unpaired t test and the Mantel-Cox test were used for statistical analyses, with a significance level of .05. RESULTS: Focused ultrasound significantly enhanced the penetration of BCNU through the BBB in normal (by 340%) and tumor-implanted (by 202%) brains without causing hemorrhaging. Treatment of tumor-implanted rats with focused ultrasound alone had no beneficial effect on tumor progression or on animal survival up to 60 days. Administration of BCNU only transiently controlled tumor progression; nevertheless, relative to untreated controls, animal survival was improved by treatment with BCNU alone (increase in median survival time [IST(median)], 15.7%, P = .023). Treatment with focused ultrasound before BCNU administration controlled tumor progression (day 31: 0.05 cm(3) + or - 0.1 [standard deviation] vs 0.28 cm(3) + or - 0.1) and improved animal survival relative to untreated controls (IST(median), 85.9%, P = .0015). CONCLUSION: This study demonstrates a means of increasing localized chemotherapeutic drug delivery for brain tumor treatment and strongly supports the feasibility of this treatment in a clinical setting.

A colorimetric immunosensor based on self-linkable dual-nanozyme for ultrasensitive bladder cancer diagnosis and prognosis monitoring.

We developed self-linkable Prussian blue (PB)-incorporated magnetic graphene oxide (PMGO) as a peroxidase-mimicking nanozyme with high oxidizability to 3,3',5,5'-tetramethylbenzidine (TMB), which generates significant absorption intensity for the colorimetric immunosensing of apolipoprotein A1 (ApoA1) in early bladder cancer (BC) diagnosis and prognosis monitoring. The ultrasensitive immunosensor was constructed using an ApoA1 antibody (AbApoA1)-functionalized chip (biochipApoA1) and self-linkable peroxidase-mimicking, PB-incorporated magnetic graphene oxide (PMGO). After incubating the sample and capturing ApoA1 proteins captured on the biochipApoA1, the PMGO was functionalized with AbApoA1, and then mouse IgG (PMGO-1), rabbit anti-mouse IgG antibody (PMGO-2), and goat anti-rabbit IgG antibody (PMGO-3) were added together. We envisioned that each captured ApoA1 protein would allow the retention of a large amount of PMGO through a self-linking process to amplify the colorimetric signal of TMB in the presence of H2O2. The linear detection range could be obviously widened in the presence of self-linkable PMGO-from 0.05 ng/mL to 100 ng/mL-compared with the group without signal amplification (from 1 ng/mL to 100 ng/mL). Our immunosensor analysis of ApoA1 in the urine of BC patients and healthy individuals was highly correlated with enzyme-linked immunosorbent assay measurements; moreover, the ApoA1 concentrations of patients with high-grade BC were significantly higher than those of patients with low-grade BC. After standard clinical treatment, a significant drop of ApoA1 concentration occurred in urine that was lower than the cut-off concentration, suggesting potential clinical applications of the new self-linkable PMGO-generating colorimetric immunosensor in early BC diagnosis and prognosis monitoring.

Fabrication of a Nanogold-Dot Array for Rapid and Sensitive Detection of Vascular Endothelial Growth Factor in Human Serum.

A simple and accurate device for early detection of malignancies is paramount for prompt treatment and prevention of metastases. In this study, we describe a novel fabrication method for producing an ordered nanogold-dot array with strong localized surface plasmon resonance (LSPR) and narrow bandwidth. The array was used as an optical biosensing chip for the detection of vascular endothelial growth factor 165 (VEGF165) in human serum. The biochip was constructed by conjugating an anti-VEGF antibody, a specific biorecognition element for VEGF165, onto the array via the fragment crystallizable (Fc) region of the antibody, ultimately increasing the efficiency of VEGF165 detection. The resulting biochip was sensitive, had a wide linear detection range (0.01-100 ng/mL), was specific for VEGF165 (showing no interference when challenged with glucose and ascorbic acid), and characterized by an excellent stability (allowing storage and transportation at room temperature). Owing to the good correlations of VEGF165 measurements obtained with ELISA, we believe that our chip holds promise as a tool for early diagnosis of cancer.

Non-invasive, neuron-specific gene therapy by focused ultrasound-induced blood-brain barrier opening in Parkinson's disease mouse model.

Focused ultrasound (FUS)-induced with microbubbles (MBs) is a promising technique for noninvasive opening of the blood-brain barrier (BBB) to allow targeted delivery of therapeutic substances into the brain and thus the noninvasive delivery of gene vectors for CNS treatment. We have previously demonstrated that a separated gene-carrying liposome and MBs administration plus FUS exposure can deliver genes into the brain, with the successful expression of the reporter gene and glial cell line-derived neurotrophic factor (GDNF) gene. In this study, we further modify the delivery system by conjugating gene-carrying liposomes with MBs to improve the GDNF gene-delivery efficiency, and to verify the possibility of using this system to perform treatment in the 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced animal disease model. FUS-BBB opening was verified by contrast-enhanced MRI, and GFP gene expression was verified via in vivo imaging system (IVIS). Western blots as well as enzyme-linked immunosorbent assay (ELISA) were conducted to measure protein expression, and immunohistochemistry (IHC) was conducted to test the Tyrosine hydroxylase (TH)-neuron distribution. Dopamine (DA) and its metabolites as well as dopamine active transporter (DAT) were quantitatively analyzed to show dopaminergic neuronal dopamine secretion/activity/metabolism. Motor performance was evaluated by rotarod test weekly. Results demonstrated that the LpDNA-MBs (gene-liposome-MBs) complexes successfully serve as gene carrier and BBB-opening catalyst, and outperformed the separated LpDNA/MBs administration both in terms of gene delivery and expression. TH-positive IHC and measurement of DA and its metabolites DOPAC and HVA confirmed improved neuronal function, and the proposed system also provided the best neuroprotective effect to retard the progression of motor-related behavioral abnormalities. Immunoblotting and histological staining further confirmed the expression of reporter genes in neuronal cells. This study suggests that FUS exposures with the administration of LpDNA-MBs complexes synergistically can serve as an effective gene therapy strategy for MPTP-animal treatment, and may have potential for further application to perform gene therapy for neurodegenerative disease.

A sensitive and selective magnetic graphene composite-modified polycrystalline-silicon nanowire field-effect transistor for bladder cancer diagnosis.

In this study, we describe the urinary quantification of apolipoprotein A II protein (APOA2 protein), a biomarker for the diagnosis of bladder cancer, using an n-type polycrystalline silicon nanowire field-effect transistor (poly-SiNW-FET). The modification of poly-SiNW-FET by magnetic graphene with long-chain acid groups (MGLA) synthesized via Friedel-Crafts acylation was compared with that obtained using short-chain acid groups (MGSA). Compared with MGSA, the MGLA showed a higher immobilization degree and bioactivity to the anti-APOA2 antibody (Ab) due to its lower steric hindrance. In addition, the magnetic properties enabled rapid separation and purification during Ab immobilization, ultimately preserving its bioactivity. The Ab-MGLA/poly-SiNW-FET exhibited a linear dependence of relative response to the logarithmical concentration in a range between 19.5pgmL(-1) and 1.95µgmL(-1), with a limit of detection (LOD) of 6.7pgmL(-1). An additional washing step before measurement aimed at excluding the interfering biocomponents ensured the reliability of the assay. We conclude that our biosensor efficiently distinguishes mean values of urinary APOA2 protein concentrations between patients with bladder cancer (29-344ngmL(-1)) and those with hernia (0.425-9.47ngmL(-1)).

Amphiphilic polyesters bearing pendant sugar moieties: synthesis, characterization, and cellular uptake.

Ring-opening polymerization (ROP) and "click" reactions were used to prepare a series of amphiphilic block-graft (PαN3CL-g-Sugar)-b-PCL polymers. The glycosylated RO-(PαN3CL-g-Sugar)-b-PCL polymers formed micelles with critical micelle concentrations (CMCs) in the range of 4.9-23.2 mg L(-1) in the aqueous phase. The mean diameters of the micelles were between 21 nm and 125 nm, considerably lower than the 200 nm diameter at which the uptake of micelles by the reticuloendothelial cells becomes compromised. Selective lectin-binding experiments confirmed that glycosylated RO-(PαN3CL-g-Sugar)-b-PCL can be used in biorecognition applications, and in vitro cell-viability assay showed that RO-(PαN3CL-g-Sugar)-b-PCL has low cytotoxicity. Micelles loaded with doxorubicin (DOX) facilitated an improved uptake of DOX by HeLa cells that was completed within 1h, and the endocytosed-DOX successfully reached intracellular compartments and entered nuclei.

Reusable sensor based on high magnetization carboxyl-modified graphene oxide with intrinsic hydrogen peroxide catalytic activity for hydrogen peroxide and glucose detection.

We propose a new strategy to improve the enzyme stability, construction and sensitivity of a multifunctional sensor. An exfoliated graphene oxide sheet with carboxyl-long-chains (GO-CLC) was prepared in one step from primitive graphite via Friedel-Crafts acylation. Magnetic nanoparticles, glucose oxidase (GOD) and poly[aniline-co-N-(1-one-butyric acid) aniline] (SPAnH) were then incorporated to form an electrochemical film (SPAnH-HMGO-CLC-GOD) for the detection of hydrogen peroxide (H(2)O(2)) and glucose. The GO and Fe(3)O(4) have intrinsic hydrogen peroxide catalytic activity and the activity will be enhanced by the combination of SPAnH coating and induces an amplification of electrochemical reduction current. This response can be used as a glucose sensor by tracing the released H(2)O(2) after enzymatic reaction of bound GOD. Our sensor was linear within the range from 0.01 mM to 1mM H(2)O(2) and 0.1mM to 1.4mM glucose, with high sensitivities of 4340.6 µA mM(-1) cm(-2) and 1074.6 µA mM(-1) cm(-2), respectively. The relative standard deviations (RSD) were 5.4% for H(2)O(2) detection and 5.8% for glucose detection. The true detecting range was 0.4-40 mM for H(2)O(2) and 4-56 mM for glucose, which multiplied by 40-fold of dilution. This sensor based on the catalysis of organic SPAnH and the enzymatic activity of GOD can be used for both H(2)O(2) and glucose sensing in potential clinical, environmental and industrial applications.

High-κ GdTixOy sensing membrane-based electrolyte-insulator-semiconductor with magnetic nanoparticles as enzyme carriers for protein contamination-free glucose biosensing.

This paper reports an electrolyte-insulator-semiconductor (EIS) device featuring a novel high-κ GdTixOy sensing membrane for high-performance pH sensing and glucose biosensing. The effect of the annealing temperature (700, 800, or 900°C) on the sensing properties of the GdTixOy membranes was investigated. The GdTixOy EIS device annealed at 900°C exhibited the greatest pH sensing performance, including the highest sensitivity (62.12mV/pH), the smallest hysteresis voltage (5mV), and the lowest drift rate (0.4mV/h), presumably because of its well-crystallized GdTixOy structure. To overcome the problems typically encountered during the practical application of biosensors (e.g., protein adsorption; preservation of enzymatic activity), we employed Fe3O4-based magnetic nanoparticles (MNPs) as enzyme carriers. The adsorption of serum protein on the unmodified sensing membrane led to poor EIS-based pH sensing (r(2)=0.71); the performance was greatly improved, however, after attaching the MNPs to the sensing membrane, thereby blocking protein adsorption significantly (by 98%) and allowing excellent pH sensing (r(2)=0.99). Moreover, we prepared a hybrid configuration of the proposed GdTixOy membrane-EIS, with magnetically attached glucose oxidase-immobilized MNPs, for glucose biosensing. The use of MNPs as enzyme carriers effectively preserved the enzymatic activity of glucose oxidase, with 45.3% of the original enzymatic activity retained after 120h of storage at 4°C (compared with complete loss of the free enzyme's activity under the same storage conditions). In addition, the proposed biosensor exhibited superior detection sensitivity of 11.03mV/mM relative to that (8.17mV/mM) obtained using the conventional enzyme immobilization method. Finally, we established the accuracy of the proposed method for blood glucose measurement; gratifyingly, blood glucose detection was comparable with the high-sensitivity glucose quantification obtained using a commercial glucose assay kit.

A colloidal suspension of nanostructured poly(N-butyl benzimidazole)-graphene sheets with high oxidase yield for analytical glucose and choline detections.

A colloidal suspension of nanostructured poly(N-butyl benzimidazole)-graphene sheets (PBBIns-Gs) was used to modify a gold electrode to form a three-dimensional PBBIns-Gs/Au electrode that was sensitive to hydrogen peroxide (H2O2) in the presence of acetic acid (AcOH). The positively charged nanostructured poly(N-butyl benzimidazole) (PBBIns) separated the graphene sheets (Gs) and kept them suspended in an aqueous solution. Additionally, graphene sheets (Gs) formed "diaphragms" that intercalated Gs, which separated PBBIns to prevent tight packing and enhanced the surface area. The PBBIns-Gs/Au electrode exhibited superior sensitivity toward H2O2 relative to the PBBIns-modified Au (PBBIns/Au) electrode. Furthermore, a high yield of glucose oxidase (GOD) on the PBBIns-Gs of 52.3mg GOD per 1mg PBBIns-Gs was obtained from the electrostatic attraction between the positively charged PBBIns-Gs and negatively charged GOD. The non-destructive immobilization of GOD on the surface of the PBBIns-Gs (GOD-PBBIns-Gs) retained 91.5% and 39.2% of bioactivity, respectively, relative to free GOD for the colloidal suspension of the GOD-PBBIns-Gs and its modified Au (GOD-PBBIns-Gs/Au) electrode. Based on advantages including a negative working potential, high sensitivity toward H2O2, and non-destructive immobilization, the proposed glucose biosensor based on an GOD-PBBIns-Gs/Au electrode exhibited a fast response time (5.6s), broad detection range (10µM to 10mM), high sensitivity (143.5µAmM(-1)cm(-2)) and selectivity, and excellent stability. Finally, a choline biosensor was developed by dipping a PBBIns-Gs/Au electrode into a choline oxidase (ChOx) solution for enzyme loading. The choline biosensor had a linear range of 0.1µM to 0.83mM, sensitivity of 494.9µAmM(-1)cm(-2), and detection limit of 0.02µM. The results of glucose and choline measurement indicate that the PBBIns-Gs/Au electrode provides a useful platform for the development of oxidase-based biosensors.

Preparation of highly conjugated water-dispersible graphene-butyric acid for the enhancement of electron transfer within polyamic acid-benzoxazole: potential applications in electrochemical sensing.

To break through the long time and complex procedures for the preparation of highly conjugated reduced graphene oxide (r-GO) in developing electrochemical sensor, a time-saving and simple method is investigated in this study. One novel step of the exfoliated accompanying carboxylated graphene sheet from pristine is achieved via Friedel-Crafts acylation. By electrophilic aromatic substitution, the succinic anhydride ring is opened and attaches covalently to the graphene sheet (Gs) to form exfoliated graphene with grafted 1-one-butyric acid (Gs-BA). The grafting chain converts anions in aqueous solution to maintain Gs-BA in a stable dispersion and noticeably decreases the π-π stacking of the exfoliated Gs during the drying process. The analytical results of the absorption spectroscopy demonstrate that the conjugation of Gs-BA is not significantly destroyed by this chemical modification; Gs-BA retains the Gs electrical properties favorable for developing electrochemical sensors. When polyamic acid-benzoxazole (PAA-BO), a hydrogen peroxide (H2O2)-sensitive probe, hybridizes with Gs-BA to form Gs-BA-PAA-BO, the electron transfer rate relating to the response time improves markedly from 1.09 s(-1) to 38.8 s(-1). Additionally, it offers a high performance for H2O2 sensing in terms of sensitivity and response time, making this method applicable for developing glucose and choline biosensors.

Magnetic gold-nanorod/ PNIPAAmMA nanoparticles for dual magnetic resonance and photoacoustic imaging and targeted photothermal therapy.

Nanomedicine can provide a multi-functional platform for image-guided diagnosis and treatment of cancer. Although gold nanorods (GNRs) have been developed for photoacoustic (PA) imaging and near infra-red (NIR) photothermal applications, their efficiency has remained limited by low thermal stability. Here we present the synthesis, characterization, and functional evaluation of non-cytotoxic magnetic polymer-modified gold nanorods (MPGNRs), designed to act as dual magnetic resonance imaging (MRI) and PA imaging contrast agents. In addition, their high magnetization allowed MPGNRs to be actively localized and concentrated by targeting with an external magnet. Finally, MPGNRs significantly enhanced the NIR-laser-induced photothermal effect due to their increased thermal stability. MPGNRs thus provide a promising new theranostic platform for cancer diagnosis and treatment by combining dual MR/PA imaging with highly effective targeted photothermal therapy.

Non-invasive synergistic treatment of brain tumors by targeted chemotherapeutic delivery and amplified focused ultrasound-hyperthermia using magnetic nanographene oxide.

The combination of chemo-thermal therapy is the best strategy to ablate tumors, but how to heat deep tumor tissues effectively without side-damage is a challenge. Here, a systemically delivered nanocarrier is designed with multiple advantages, including superior heat absorption, highly efficient hyperthermia, high drug capacity, specific targeting ability, and molecular imaging, to achieve both high antitumor efficacy and effective amplification of hyperthermia with minimal side effects.

Potential of magnetic nanoparticles for targeted drug delivery.

Nanoparticles (NPs) play an important role in the molecular diagnosis, treatment, and monitoring of therapeutic outcomes in various diseases. Their nanoscale size, large surface area, unique capabilities, and negligible side effects make NPs highly effective for biomedical applications such as cancer therapy, thrombolysis, and molecular imaging. In particular, nontoxic superparamagnetic magnetic NPs (MNPs) with functionalized surface coatings can conjugate chemotherapeutic drugs or be used to target ligands/proteins, making them useful for drug delivery, targeted therapy, magnetic resonance imaging, transfection, and cell/protein/DNA separation. To optimize the therapeutic efficacy of MNPs for a specific application, three issues must be addressed. First, the efficacy of magnetic targeting/guidance is dependent on particle magnetization, which can be controlled by adjusting the reaction conditions during synthesis. Second, the tendency of MNPs to aggregate limits their therapeutic use in vivo; surface modifications to produce high positive or negative charges can reduce this tendency. Finally, the surface of MNPs can be coated with drugs which can be rapidly released after injection, resulting in targeting of low doses of the drug. Drugs therefore need to be conjugated to MNPs such that their release is delayed and their thermal stability enhanced. This chapter describes the creation of nanocarriers with a high drug-loading capacity comprised of a high-magnetization MNP core and a shell of aqueous, stable, conducting polyaniline derivatives and their applications in cancer therapy. It further summarizes some newly developed methods to synthesize and modify the surfaces of MNPs and their biomedical applications.

Bioconjugation of recombinant tissue plasminogen activator to magnetic nanocarriers for targeted thrombolysis.

Low-toxicity magnetic nanocarriers (MNCs) composed of a shell of poly [aniline-co-N-(1-one-butyric acid) aniline] over a Fe(3)O(4) magnetic nanoparticle core were developed to carry recombinant tissue plasminogen activator (rtPA) in MNC-rtPA for targeted thrombolysis. With an average diameter of 14.8 nm, the MNCs exerted superparamagnetic properties. Up to 276 µg of active rtPA was immobilized per mg of MNCs, and the stability of the immobilized rtPA was greatly improved during storage at 4°C and 25°C. In vitro thrombolysis testing with a tubing system demonstrated that magnet-guided MNC-rtPA showed significantly improved thrombolysis compared with free rtPA and reduced the clot lysis time from 39.2 ± 3.2 minutes to 10.8 ± 4.2 minutes. In addition, magnet-guided MNC-rtPA at 20% of the regular rtPA dose restored blood flow within 15-25 minutes of treatment in a rat embolism model without triggering hematological toxicity. In conclusion, this improved system is based on magnetic targeting accelerated thrombolysis and is potentially amenable to therapeutic applications in thromboembolic diseases.