Rung-Ywan Tsai

The effectiveness of a magnetic nanoparticle-based delivery system for BCNU in the treatment of gliomas

This study describes the creation and characterization of drug carriers prepared using the polymer poly[aniline-co-N-(1-one-butyric acid) aniline] (SPAnH) coated on Fe(3)O(4) cores to form three types of magnetic nanoparticles (MNPs); these particles were used to enhance the therapeutic capacity and improve the thermal stability of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), a compound used to treat brain tumors. The average hydrodynamic diameter of the MNPs was 89.2 ± 8.5 nm and all the MNPs displayed superparamagnetic properties. A maximum effective dose of 379.34 μg BCNU could be immobilized on 1 mg of MNP-3 (bound-BCNU-3). Bound-BCNU-3 was more stable than free-BCNU when stored at 4 °C, 25 °C or 37 °C. Bound-BCNU-3 could be concentrated at targeted sites in vitro and in vivo using an externally applied magnet. When applied to brain tumors, magnetic targeting increased the concentration and retention of bound-BCNU-3. This drug delivery system promises to provide more effective tumor treatment using lower therapeutic doses and potentially reducing the side effects of chemotherapy.

Magnetic-nanoparticle-modified paclitaxel for targeted therapy for prostate cancer

A nontoxic drug nanocarrier containing carboxyl groups was successfully developed by mixing magnetic nanoparticles (MNPs) of Fe(3)O(4) with the water-soluble polyaniline derivative poly[aniline-co-sodium N-(1-one-butyric acid) aniline] (SPAnNa) and doping with HCl aqueous solution to form SPAnH/MNPs shell/core. SPAnH/MNPs could be used to effectively immobilize the hydrophobic drug paclitaxel (PTX), thus enhancing the drugs thermal stability and water solubility. Up to 302.75 mug of PTX could be immobilized per mg of SPAnH/MNPs. SPAnH/MNPs-bound-PTX (bound-PTX) was more stable than free-PTX at both 25 degrees C and 37 degrees C. Furthermore, bound-PTX was more cytotoxic to human prostate carcinoma cells (PC3 and CWR22R) than free-PTX at 37 degrees C, and the inhibition of cellular growth was even more pronounced when magnetic targeting was applied to the bound-PTX. These data indicate that this magnetically targeted drug delivery system provides more effective treatment of prostate cancer cells using lower therapeutic doses and thus with potentially fewer side-effects.

Superhigh-magnetization nanocarrier as a doxorubicin delivery platform for magnetic targeting therapy

The aim of this study describes the creation of superhigh-magnetization nanocarriers (SHMNCs) comprised of a magnetic Fe(3)O(4) (SHMNPs) core and a shell of aqueous stable self-doped poly[N-(1-one-butyric acid)]aniline (SPAnH), which have a high drug loading capacity (∼27.1 wt%) of doxorubicin (DOX). The SHMNCs display superparamagnetic property with a magnetization of 89.7 emu/g greater than that of Resovist (a commercial contrast agent used for magnetic resonance imaging; 73.7 emu/g). Conjugating the anticancer drug DOX to these nanocarriers enhances the drugs thermal stability and maximizes the efficiency with which it is delivered by magnetic targeting (MT) therapy to MGH-U1 bladder cancer cells, in part by avoiding the effects of p-glycoprotein (P-gp) pumps to enhance the intracellular concentration of DOX. The high R2 relaxivity (434.7 mM(-1)s(-1)) of SHMNCs not only be a most effective MT carrier of chemotherapeutic agent but be an excellent contrast agent of MRI, allowing the assessment of the distribution and concentration of DOX in various tissues and organs. This advanced drug delivery system promises to provide more effective MT therapy and tumor treatment using lower therapeutic doses and potentially reducing the side effects of cardiotoxicity caused by DOX.

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.

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.

Self-protecting core-shell magnetic nanoparticles for targeted, traceable, long half-life delivery of BCNU to gliomas

The successful delivery of anti-cancer drugs relies on the simultaneous capability to actively target a specific location, a sufficient lifetime in the active form in the circulation, and traceability and quantification of drug distribution via in vivo medical imaging. Herein, a highly magnetic nanocarrier (HMNC) composed of an Fe(3)O(4) core and an aqueous-stable, self-doped poly[N-(1-one-butyric acid)]aniline (SPAnH) shell was chemically synthesized. This nanocarrier exhibited a high capacity for 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) drug loading. BCNU and o-(2-aminoethyl)polyethylene glycol (EPEG) were covalently immobilized on the surface of the HMNC to form a self-protecting magnetic nanomedicine (i.e., SPMNM) that could simultaneously provide low reticuloendothelial system uptake, high active-targeting, and in vivo magnetic resonance imaging (MRI) traceability. Meanwhile, the SPMNM was found to reduce the phagocytosis by macrophages and reduce the hydrolysis rate of BCNU. The high magnetization (approximately 1.2-fold higher than Resovist) of the HMNC allowed efficient magnetic targeting to the tumor. The synergetic drug delivery approach provided approximately a 3.4-fold improvement of the drugs half-life (from 18 h to 62 h) and significantly prolonged the median survival rate in animals that received a low dose of BCNU, compared with those that received a high dose of free BCNU (63 days for those that received 4.5 mg BCNU/kg carried by the nanocarrier versus 50 days for those that received 13.5 mg of free-BCNU). This improvement could enhance the potential of magnetic targeting therapy in clinical applications of cancer treatments.

The intrinsic redox reactions of polyamic acid derivatives and their application in hydrogen peroxide sensor.

Polyamic acids (PAAs) containing benzothiazole (BT) and benzoxazole (BO) pendent groups (PAA-BT and PAA-BO, respectively) which possessed electroactivity were synthesized successfully. The addition of H(2)O(2) chemically oxidized the intrinsic carboxylic acid groups of PAA to form peroxy acid groups, and the peroxy acid further oxidized the electroactive sites of BT and BO to form N-oxides. The N-oxides could be reverted to their original form by electrochemical reduction, thus increasing the electrochemical reductive current. Based on this mechanism, enzyme-free hydrogen peroxide (H(2)O(2)) biosensors were prepared by modifying gold electrodes with the PAA derivatives (PAA-BT/Au and PAA-BO/Au, respectively). These biosensors had rapid response times (3.9-5.2 s) and high selectivity and sensitivity (280.6-311.2 μA/mM-cm(2)). A comparison of the PAA-BT/Au and PAA-BO/Au electrodes with electrodes prepared using polyamide-BT or polyamide-BO (i.e., lacking the carboxylic acid groups) confirmed the mechanism by which PAA derivatives detect H(2)O(2). Modifying the surface morphology of the electrode from a planar to a three-dimensional (3D) configuration enhanced the performance of the PAA-BO/Au electrode. The sensitivity of the 3D-PAA-BO/Au electrode was 1394.9 μA/mM-cm(2), ∼ 4.5 times higher than that of the planar electrode. The detection limit was also enhanced from 5.0 to 1.43 μM. The biosensor was used analytically to detect and measure H(2)O(2) in urine samples collected from healthy individuals and patients suffering from noninvasive bladder cancer. The results were promising and comparable to that measured by a classical HPLC method, which verified the developed biosensor had a potential to provide a usefully analytical approach for bladder cancer.

Cooperative dual-activity targeted nanomedicine for specific and effective prostate cancer therapy.

A key issue in cancer therapy is how to enhance the tumor-targeting efficacy of chemotherapeutic agents. In this study, we developed a cooperative dual-targeted delivery platform for paclitaxel (PTX) that has potential application as a powerful prostate cancer treatment. The nanomedicine was prepared by first conjugating PTX to nontoxic high-magnetization nanocarriers which can be actively guided and targeted by an external magnet. Next, the surface was functionalized with carboxylated o-(2-aminoethyl)polyethyleneglycol (NH(2)-EPEG-COOH) to enable uptake by the reticuloendothelial system. Antiprostate-specific membrane antigen antibodies (APSMAs) were then conjugated onto the carrier to recognize the extracellular domain of the prostate-cancer specific membrane antigen (PSMA), thus binding to cancer cells as a secondary active targeting mechanism. We found a significant enhancement of PTX concentration at the tumor site by nearly 20-fold. In addition, the drug half-life was prolonged more than 4.1-fold (from 24 to 99 h) at 37 °C. Low-dose (4.5 mg/kg) injection of the dual-targeted therapeutic nanomedicine in the presence of magnetic targeting significantly prolonged the median survival of nude mice from 35 to 58 days compared to mice that received a high dose (6 mg/kg) of free PTX. This report demonstrates the potential utility of targeted nanomedicine in the clinical treatment of cancer.

Synthesis and characterization of carboxylated polybenzimidazole and its use as a highly sensitive and selective enzyme-free H2O2 sensor

A novel polyelectrolyte, poly[N-(1-one-butyric acid)benzimidazole] (PBI-BA), was synthesized and used to fabricate an amperometric hydrogen peroxide (H2O2) sensor. It was found that PBI-BA can be oxidized by H2O2 and produce a current response during electrochemical reduction. This mechanism was used to develop an enzyme-free H2O2 sensor. Under optimal experimental conditions, the sensor showed high reproducibility, selectivity and stability. The stability of the PBI-BA electrode after annealing at 100 °C was also studied. Interestingly, the sensitivity of the modified electrode was 15.2% higher than that without heat treatment. The sensor was sensitive toward H2O2 over a linear range from 6.2 μM to 5.0 mM with a detection limit of 3.1 μM. Because graphene sheets (Gs) suspend readily in the polyelectrolyte solution, a PBI-BA–Gs/Au electrode was also fabricated, improving the sensors performance dramatically: this sensor detected H2O2 over a linear range of 2.5 μM to 5 mM, with a correlation coefficient of 0.998 (n = 5) and a sensitivity of 1056 μA mM−1 cm−2.

Water dispersible 1-one-butyric acid-functionalised multi-walled carbon nanotubes for enzyme immobilisation and glucose sensing

A new approach to synthesising 1-one-butyric acid-functionalised multi-walled carbon nanotubes (MWCNTs-BA) is presented involving the surface modification of multi-walled carbon nanotubes (MWCNTs) via a Friedel–Crafts chemical oxidative reaction using succinic anhydride in aluminium chloride. The MWCNTs-BA disperse homogeneously in water and exhibit very good solubility. Fourier transform infrared, Raman and X-ray photoelectron spectra indicated that the 1-one-butyric acid (BA) groups had formed on the sidewalls of the MWCNTs. The percentage of BA groups in the MWCNTs-BA was 7.80 mol% as determined using a simple acid–base titration method. The electrical conductivity, morphology and structure of the MWCNTs-BA were characterised with a four-point probe, field-emission scanning electron microscopy, transmission electron microscopy and X-ray diffraction. Furthermore, the sensor created by the immobilisation of glucose oxidase (GOD) onto the surface of MWCNTs-BA was sensitive toward glucose over a linear range from 10 μM to 2.5 mM with a correlation coefficient of 0.999 (n = 5), and it showed good sensitivity (23.5 μA mM−1 cm−2), enzyme affinity, reproducibility and storage stability. This immobile MWCNTs-BA matrix acts as an electron bridge between the enzyme molecules and the electrode, and it has the potential to allow the construction of useful sensors through enzyme immobilisation.