RESUMO
Amateurs often struggle with detecting and quantifying protein biomarkers in body fluids due to the high expertise required. This study introduces a Lab-in-a-Vial (LV) rapid diagnostic platform, featuring hydrangea-like platinum nanozymes (PtNH), for rapid, accurate detection and quantification of protein biomarkers on-site within 15 min. This method significantly enhances detection sensitivity for various biomarkers in body fluids, surpassing traditional methods such as enzyme-linked immunosorbent assays (ELISA) and lateral flow assays (LFA) by ≈250 to 1300 times. The LV platform uses a glass vial coated with specific bioreceptors such as antigens or antibodies, enabling rapid in vitro evaluation of disease risk from small fluid samples, similar to a personal ELISA-like point-of-care test (POCT). It overcomes challenges in on-site biomarker detection, allowing both detection and quantification through a portable wireless spectrometer for healthcare internet of things (H-IoT). The platform's effectiveness and adaptability are confirmed using IgG/IgM antibodies from SARS-CoV-2 infected patients and nuclear matrix protein (NMP22) from urothelial carcinoma (UC) patients as biomarkers. These tests demonstrated its accuracy and flexibility. This approach offers vast potential for diverse disease applications, provided that the relevant protein biomarkers in bodily fluids are identified.
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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.
Assuntos
Anticorpos Monoclonais Humanizados/química , Técnicas Biossensoriais , Antígeno Ca-125/sangue , Carcinoma/diagnóstico , Proteínas de Membrana/sangue , Neoplasias do Colo do Útero/diagnóstico , Fator A de Crescimento do Endotélio Vascular/sangue , Anticorpos Monoclonais Humanizados/imunologia , Bevacizumab , Antígeno Ca-125/análise , Carcinoma/sangue , Carcinoma/imunologia , Carcinoma/patologia , Feminino , Óxido Ferroso-Férrico/química , Humanos , Imãs , Proteínas de Membrana/análise , Nanofios/química , Estadiamento de Neoplasias , Silício/química , Tomografia Computadorizada por Raios X , Transistores Eletrônicos , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/patologiaRESUMO
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.
Assuntos
Técnicas Biossensoriais , Peróxido de Hidrogênio/análise , Resinas Acrílicas/química , Compostos de Anilina/química , Condutividade Elétrica , Eletroquímica/métodos , Eletrodos , Desenho de Equipamento , Humanos , Peróxido de Hidrogênio/química , Teste de Materiais , Modelos Químicos , Óxidos/química , Polímeros/química , Porosidade , Sensibilidade e Especificidade , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Propriedades de SuperfícieRESUMO
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.
Assuntos
Nanoestruturas , Técnicas Biossensoriais , Ouro , Humanos , Análise em Microsséries , Neoplasias , Ressonância de Plasmônio de Superfície , Fator A de Crescimento do Endotélio VascularRESUMO
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)).
Assuntos
Apolipoproteína A-II/urina , Técnicas Biossensoriais/métodos , Nanofios/química , Neoplasias da Bexiga Urinária/urina , Grafite/química , Humanos , Silício/química , Neoplasias da Bexiga Urinária/patologiaRESUMO
A compact and position-addressable blue ray scanning microscope (BSM) based on a commercially available Blu-ray disk pickup head (PUH) is developed for cell imaging with high resolution and low cost. The BSM comprises two objective lenses with numerical apertures (NAs) of 0.85 and 0.6 for focusing blue and red laser beams, respectively, on the sample slide. The blue and red laser beams are co-located adjacent to each other and move synchronously. A specially designed sample slide is used with a sample area and an address-patterned area for sample holding and address recognition, respectively. The blue laser beam is focused on the sample area and is used for fluorescent excitation and image capturing, whereas the red laser beam is focused on the address-patterned area and is used for address recognition and dynamic focusing. The address-patterned area is divided into 310 sectors. The cell image of each sector of the sampling area has a corresponding address pattern. Fluorescence images of monkey-derived kidney epithelial cells and fibroblast cells in which the F-actin is stained with fluorophore phalloidin CF 405 are measured by the BSM, with results comparable to those measured by a Leica TCS CP2 confocal microscope. The cell image of an area of interest can be easily tracked based on the coded address, and a large-area sample image can be accurately reconstructed from the sector images.
RESUMO
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.
Assuntos
Benzimidazóis/química , Técnicas de Química Analítica/métodos , Colina/análise , Coloides/química , Glucose/análise , Grafite/química , Nanoestruturas/química , Peroxidase/química , Eletrodos , Estrutura Molecular , Tamanho da Partícula , Polímeros/química , Reprodutibilidade dos TestesRESUMO
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.
Assuntos
Técnicas Biossensoriais/instrumentação , Condutometria/instrumentação , Glucose Oxidase/química , Glucose/análise , Grafite/química , Peróxido de Hidrogênio/análise , Nanopartículas de Magnetita/química , Catálise , Eletrodos , Enzimas Imobilizadas/química , Desenho de Equipamento , Análise de Falha de Equipamento , Reutilização de Equipamento , Nanopartículas de Magnetita/ultraestrutura , Óxidos/química , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
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.
Assuntos
Derivados de Benzeno/química , Benzoxazóis/química , Ácido Butírico/química , Técnicas Eletroquímicas/métodos , Grafite/química , Peróxido de Hidrogênio/análise , Polímeros/química , Técnicas Biossensoriais/métodos , Catálise , Colina/análise , Eletrodos , Transporte de Elétrons , Elétrons , Glucose/análise , Ouro/química , Sensibilidade e EspecificidadeRESUMO
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.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/terapia , Grafite/química , Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Imãs/química , Nanoestruturas/uso terapêutico , Óxidos/química , Animais , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Transformação Celular Neoplásica , Portadores de Fármacos/química , Portadores de Fármacos/uso terapêutico , Imageamento por Ressonância Magnética , Camundongos , Nanoestruturas/química , Polietilenoglicóis/químicaRESUMO
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.
Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Coagulação Sanguínea/fisiologia , Separação Imunomagnética/métodos , Nanopartículas de Magnetita/química , Nanocápsulas/química , Ativador de Plasminogênio Tecidual/administração & dosagem , Ativador de Plasminogênio Tecidual/química , Animais , Fibrinolíticos/administração & dosagem , Fibrinolíticos/química , Humanos , Nanopartículas de Magnetita/administração & dosagem , Nanopartículas de Magnetita/ultraestrutura , Teste de Materiais , Nanocápsulas/administração & dosagem , Nanocápsulas/ultraestrutura , Ligação Proteica , RatosRESUMO
Multidrug resistance (MDR) presents a major obstacle to curing cancer. Chemotherapy failure can occur through both cell membrane drug resistance (CMDR) and nuclear drug resistance (NDR), and anticancer effectiveness of chemotherapeutic agents is especially reduced by their nuclear export. Here we report an exciting magnetically-targeted nanomedicine formed by conjugation of epirubicin (EPI) to non-toxic and high-magnetization nanocarrier (HMNC). Strikingly, HMNC-EPI overcomes both CMDR and NDR in human bladder cancer cell models, without using P-glycoprotein (P-gp) and nuclear pore inhibitors. Besides, the half-life of drug is prolonged ~1.8-fold (from 45 h to 81 h) at 37 °C, with a ~10-fold increase in concentration at the tumor site through magnetic targeting (MT). Moreover, malignant NDR bladder cancer can be effectively inhibited after 14 days in mice by just two injections and MT. We are the first to demonstrate the nanomedical strategy that can overcome the CMDR and NDR bladder cancers simultaneously, and proceed to the excellent MT therapy, significantly reducing the dosage and cardiotoxicity and holding great promise for incurable human MDR bladder cancer.
Assuntos
Portadores de Fármacos/química , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Epirubicina/uso terapêutico , Imageamento por Ressonância Magnética/métodos , Nanoestruturas/química , Neoplasias da Bexiga Urinária/tratamento farmacológico , Animais , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Meios de Contraste/farmacologia , Reagentes de Ligações Cruzadas/farmacologia , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Epirubicina/metabolismo , Epirubicina/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Magnetismo , Camundongos , Nanoestruturas/ultraestrutura , Imagens de Fantasmas , Distribuição Tecidual/efeitos dos fármacos , Resultado do Tratamento , Neoplasias da Bexiga Urinária/patologiaRESUMO
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.
Assuntos
Antineoplásicos/farmacologia , Terapia de Alvo Molecular/métodos , Nanomedicina/métodos , Paclitaxel/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Animais , Anticorpos Antineoplásicos/química , Anticorpos Antineoplásicos/imunologia , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Meios de Contraste , Portadores de Fármacos/química , Humanos , Imageamento por Ressonância Magnética , Imãs/química , Masculino , Camundongos , Paclitaxel/química , Paclitaxel/uso terapêutico , Polietilenoglicóis/química , Antígeno Prostático Específico/imunologia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The imine of polybenzimidazole (PBI) is chemically oxidized by hydrogen peroxide (H(2)O(2)) in the presence of acetic acid (AcOH). Fourier transform infrared (FT-IR) and X-ray photoelectron spectroscopies (XPS) showed that when the AcOH concentration remained constant, the degree of oxidation increased with increasing H(2)O(2) levels. Moreover, the imine also exhibited electrochemical redox behavior. Based on these properties, a PBI-modified Au (PBI/Au) electrode was developed as an enzyme-free H(2)O(2) sensor. At an applied potential of -0.5V vs. Ag/AgCl, the current response of the PBI/Au electrode was linear with H(2)O(2) concentration over a range from 0.075 to 1.5mM, with a sensitivity of 55.0 µA mM(-1)cm(-2). The probe had excellent stability, with <5% variation from its initial response current after storage at 50°C for 10 days. Potentially interfering species such as ascorbic or uric acid had no effect on sensitivity. Sensitivity improved dramatically when multiwalled carbon nanotubes (MWCNT) were incorporated in the probe. Under optimal conditions, the detection of H(2)O(2) using a MWCNT-PBI/Au electrode was linear from 1.56 µM to 2.5mM, with a sensitivity of 928.6 µA mM(-1)cm(-2). Analysis of H(2)O(2) concentrations in urine samples using a MWCNT-PBI/Au electrode produced accurate real-time results comparable to those of traditional HPLC methods.
Assuntos
Eletrodos , Peróxido de Hidrogênio/análise , Benzimidazóis , Técnicas Eletroquímicas , Ouro , Humanos , Peróxido de Hidrogênio/urina , Sondas Moleculares/síntese química , Nanotubos de Carbono , PolímerosRESUMO
A novel mechanism to detect hydrogen peroxide (H(2)O(2)) using a poly(N-butyl benzimidazole) (PBBI)-modified gold (PBBI/Au) electrode is proposed. Synthetic PBBI was oxidized using a mixture of acetic acid (AcOH) and H(2)O(2) to form PBBI N-oxide (PBBINO). The structure of PBBINO was verified by Fourier transform infrared spectroscopy (FT-IR) and the degree of oxidation was measured by X-ray photoelectron spectroscopy (XPS). Moreover, the oxide could be reduced electrochemically back to PBBI. Based on this reaction, a novel enzyme-free PBBI/Au electrode was developed to detect H(2)O(2) in the presence of AcOH electrochemically. The biosensor detected H(2)O(2) linearly over concentrations ranging from 25 µM to 10 mM with a detection limit of 6.25 µM in phosphate buffer solution (PBS) mixed with AcOH at pH 6.4. In addition, at an applied potential of -0.5 V, the sensor characteristics could be tuned using AcOH over a pH range of 3.7-6.4. The sensitivity of the probe could be enhanced from 35.1 to 419.4 µA mM(-1) cm(-2) by modifying the surface morphology of the PBBI/Au electrode from a smooth plane to a granular, three-dimensional configuration. Furthermore, it was not influenced by interfering compounds and showed high thermal stability.
Assuntos
Benzimidazóis/química , Técnicas Biossensoriais/métodos , Ouro/química , Peróxido de Hidrogênio/análise , Polímeros/química , Ácido Acético/química , Técnicas Eletroquímicas/métodos , Eletrodos , Concentração de Íons de Hidrogênio , Oxirredução , Ácido Úrico/químicaRESUMO
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), â¼ 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.
Assuntos
Derivados de Benzeno/química , Técnicas Biossensoriais , Peróxido de Hidrogênio/química , Oxidantes/química , Polímeros/química , Eletroquímica/métodos , Eletrodos , Ouro/química , Humanos , Limite de Detecção , Teste de Materiais , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Oxirredução , Espectroscopia Fotoeletrônica , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de Superfície , Neoplasias da Bexiga Urinária/urinaRESUMO
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 (â¼27.1 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 drug's 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.
Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacocinética , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacocinética , Sistemas de Liberação de Medicamentos/métodos , Óxido Ferroso-Férrico/química , Neoplasias da Bexiga Urinária/tratamento farmacológico , Compostos de Anilina/química , Animais , Antibióticos Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Meios de Contraste/química , Doxorrubicina/farmacologia , Humanos , Imageamento por Ressonância Magnética/métodos , Imãs/química , Camundongos , Nanoestruturas/química , Nanoestruturas/ultraestruturaRESUMO
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.
Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Carmustina/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Glioma/tratamento farmacológico , Nanopartículas/química , Animais , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/química , Carmustina/administração & dosagem , Carmustina/química , Linhagem Celular , Linhagem Celular Tumoral , Glioma/patologia , Glioma/ultraestrutura , Humanos , Imageamento por Ressonância Magnética , Masculino , Microscopia Eletrônica de Transmissão , Ratos , Ratos Sprague-DawleyRESUMO
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 drug's 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.
Assuntos
Carmustina/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Glioma/tratamento farmacológico , Nanopartículas de Magnetita/química , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carmustina/farmacologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Simulação por Computador , Reagentes de Ligações Cruzadas/farmacologia , DNA/metabolismo , Portadores de Fármacos/química , Estabilidade de Medicamentos , Meia-Vida , Humanos , Nanopartículas de Magnetita/ultraestrutura , Camundongos , Imagem Molecular , Sistema Fagocitário Mononuclear/efeitos dos fármacos , Temperatura , Resultado do TratamentoRESUMO
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 drug's 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.