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Proton therapy can treat tumors located in radiation-sensitive tissues. This article demonstrates the possibility of enhancing the proton therapy with targeted gold nanoparticles that selectively recognize tumor cells. Au-PEG nanoparticles at concentrations above 25 mg/L and 4 Gy proton dose caused complete death of EMT6/P cells in vitro. Binary proton therapy using targeted Au-PEG-FA nanoparticles caused an 80% tumor growth inhibition effect in vivo. The use of targeted gold nanoparticles is promising for enhancing the proton irradiation effect on tumor cells and requires further research to increase the therapeutic index of the approach.
Assuntos
Carcinoma de Ehrlich , Ouro , Nanopartículas Metálicas , Terapia com Prótons , Ouro/química , Ouro/farmacologia , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Terapia com Prótons/métodos , Animais , Carcinoma de Ehrlich/radioterapia , Carcinoma de Ehrlich/tratamento farmacológico , Carcinoma de Ehrlich/patologia , Camundongos , Linhagem Celular Tumoral , Polietilenoglicóis/químicaRESUMO
We studied the antitumor activity of the combined use of local proton irradiation in two modes (10 and 31 Gy) with preliminary intra-tumoral injection of two types of bismuth nanoparticles differing in surface coating: coated with the amphiphilic molecule Pluronic-F127 or Silane-PEG (5 kDa)-COOH polymer. Nanoparticles were used in doses of 0.75 and 1.5 mg/mouse. In two independent series on experimental tumor model (solid Ehrlich carcinoma), bismuth nanoparticles of both modifications injected directly into the tumor enhanced the antitumor effects of proton therapy. Moreover, the radiosensitizing effect of bismuth nanoparticles administered via this route increased with the increasing the doses of nanoparticles and the doses of radiation exposure. In our opinion, these promising data obtained for the first time extend the possibilities of treating malignant neoplasms.
Assuntos
Bismuto , Carcinoma de Ehrlich , Poloxâmero , Terapia com Prótons , Carcinoma de Ehrlich/radioterapia , Carcinoma de Ehrlich/tratamento farmacológico , Carcinoma de Ehrlich/patologia , Animais , Bismuto/uso terapêutico , Bismuto/química , Camundongos , Terapia com Prótons/métodos , Poloxâmero/química , Radiossensibilizantes/uso terapêutico , Radiossensibilizantes/química , Radiossensibilizantes/farmacologia , Polietilenoglicóis/química , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Nanopartículas/química , FemininoRESUMO
High X-ray absorption combined with photothermal properties make bismuth nanoparticles (Bi NP) a promising agent for multimodal cancer theranostics. However, the synthesis of Bi NP by the "classical" chemical methods has numerous limitations, including potential toxicity of the produced nanomaterials. Here we studied in vitro toxicity of laser-synthesized Bi NP coated with Pluronic F-127 on mouse fibroblast cell line L929. The survival of L929 cells decreased linearly with increasing the concentration of Bi NP in a concentration range of 3-500 µg/ml; the LC50 value was 57 µg/ml. The unique combination of functional properties and moderate toxicity of the laser-synthesized Bi NP makes them a new promising platform for sensitization of multimodal cancer theranostics.
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Nanopartículas Metálicas , Animais , Camundongos , Bismuto/toxicidade , Bismuto/química , Linhagem Celular Tumoral , Nanopartículas Metálicas/toxicidade , Nanopartículas Metálicas/química , Nanopartículas/toxicidade , Nanopartículas/química , Nanoestruturas , Neoplasias/metabolismo , Fototerapia/métodosRESUMO
Bismuth-based compounds are considered to be the best candidates for computed tomography (CT) imaging of gastrointestinal (GI) tract due to high X-ray absorption. Here, we report the introduction of polymer-coated bismuth oxychloride (BiOCl) nanosheets for highly efficient CT imaging in healthy mice and animal with colitis. We demonstrate simple, low cost and fast aqueous synthesis protocol which provides gram-quantity yield of chemically stable BiOCl nanosheets. The developed contrast gives 2.55-fold better CT enhancement compared to conventional contrast with negligible in vivo toxicity. As a major finding we report a regioselective CT imaging of GI tract by using nanoparticles coated with differentially charged polymers. Coating of nanoparticles with a positively charged polymer leads to their fast accumulation in small intestine, while the coating with negatively charged polymers stimulates prolonged stomach retention. We propose that this effect may be explained by a pH-controlled aggregation of nanoparticles in stomach. This feature may become the basis for advancement in clinical diagnosis of entire GI tract.
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Bismuto , Polímeros , Animais , Bismuto/química , Trato Gastrointestinal/diagnóstico por imagem , Camundongos , Raios XRESUMO
Nuclear nanomedicine, with its targeting ability and heavily loading capacity, along with its enhanced retention to avoid rapid clearance as faced with molecular radiopharmaceuticals, provides unique opportunities to treat tumors and metastasis. Despite these promises, this field has seen limited activities, primarily because of a lack of suitable nanocarriers, which are safe, excretable and have favorable pharmacokinetics to efficiently deliver and retain radionuclides in a tumor. Here, we introduce biodegradable laser-synthesized Si nanoparticles having round shape, controllable low-dispersion size, and being free of any toxic impurities, as highly suitable carriers of therapeutic 188Re radionuclide. The conjugation of the polyethylene glycol-coated Si nanoparticles with radioactive 188Re takes merely 1 hour, compared to its half-life of 17 hours. When intravenously administered in a Wistar rat model, the conjugates demonstrate free circulation in the blood stream to reach all organs and target tumors, which is radically in contrast with that of the 188Re salt that mostly accumulates in the thyroid gland. We also show that the nanoparticles ensure excellent retention of 188Re in tumor, not possible with the salt, which enables one to maximize the therapeutic effect, as well as exhibit a complete time-delayed conjugate bioelimination. Finally, our tests on rat survival demonstrate excellent therapeutic effect (72% survival compared to 0% of the control group). Combined with a series of imaging and therapeutic functionalities based on unique intrinsic properties of Si nanoparticles, the proposed biodegradable complex promises a major advancement in nuclear nanomedicine.
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Portadores de Fármacos/química , Nanomedicina , Nanopartículas/química , Radioisótopos/química , Radioisótopos/uso terapêutico , Rênio/química , Rênio/uso terapêutico , Segurança , Silício/química , Linhagem Celular Tumoral , Humanos , Medicina Nuclear , Polietilenoglicóis/química , Radioisótopos/farmacocinética , Rênio/farmacocinética , Distribuição TecidualRESUMO
When metal nanoparticles are arranged in an ordered array, they may scatter light to produce diffracted waves. If one of the diffracted waves then propagates in the plane of the array, it may couple the localized plasmon resonances associated with individual nanoparticles together, leading to an exciting phenomenon, the drastic narrowing of plasmon resonances, down to 1-2 nm in spectral width. This presents a dramatic improvement compared to a typical single particle resonance line width of >80 nm. The very high quality factors of these diffractively coupled plasmon resonances, often referred to as plasmonic surface lattice resonances, and related effects have made this topic a very active and exciting field for fundamental research, and increasingly, these resonances have been investigated for their potential in the development of practical devices for communications, optoelectronics, photovoltaics, data storage, biosensing, and other applications. In the present review article, we describe the basic physical principles and properties of plasmonic surface lattice resonances: the width and quality of the resonances, singularities of the light phase, electric field enhancement, etc. We pay special attention to the conditions of their excitation in different experimental architectures by considering the following: in-plane and out-of-plane polarizations of the incident light, symmetric and asymmetric optical (refractive index) environments, the presence of substrate conductivity, and the presence of an active or magnetic medium. Finally, we review recent progress in applications of plasmonic surface lattice resonances in various fields.
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Crystalline silicon (Si) nanoparticles present an extremely promising object for bioimaging based on photoluminescence (PL) in the visible and near-infrared spectral regions, but their efficient PL emission in aqueous suspension is typically observed after wet chemistry procedures leading to residual toxicity issues. Here, we introduce ultrapure laser-synthesized Si-based quantum dots (QDs), which are water-dispersible and exhibit bright exciton PL in the window of relative tissue transparency near 800 nm. Based on the laser ablation of crystalline Si targets in gaseous helium, followed by ultrasound-assisted dispersion of the deposited films in physiological saline, the proposed method avoids any toxic by-products during the synthesis. We demonstrate efficient contrast of the Si QDs in living cells by following the exciton PL. We also show that the prepared QDs do not provoke any cytoxicity effects while penetrating into the cells and efficiently accumulating near the cell membrane and in the cytoplasm. Combined with the possibility of enabling parallel therapeutic channels, ultrapure laser-synthesized Si nanostructures present unique object for cancer theranostic applications.
Assuntos
Meios de Contraste/química , Medições Luminescentes , Imagem Óptica/métodos , Pontos Quânticos/química , Linhagem Celular Tumoral , Humanos , Lasers , SilícioRESUMO
Electron-beam-induced deposition of titanium oxide nanopatterns is described. The precursor is titanium tetra-isopropoxide, delivered to the deposition point through a needle and mixed with oxygen at the same point via a flow through a separate needle. The depositions are free of residual carbon and have an EDX determined stoichiometry of TiO2.2. High resolution transmission electron microscopy and Raman spectroscopy studies reveal an amorphous structure of the fabricated titanium oxide. Ellipsometric characterization of the deposited material reveals a refractive index of 2.2-2.4 RIU in the spectral range of 500-1700 nm and a very low extinction coefficient (lower than 10(-6) in the range of 400-1700 nm), which is consistent with high quality titanium oxide. The electrical resistivity of the titanium oxide patterned with this new process is in the range of 10-40 GΩ cm and the measured breakdown field is in the range of 10-70 V µm(-1). The fabricated nanopatterns are important for a variety of applications, including field-effect transistors, memory devices, MEMS, waveguide structures, bio- and chemical sensors.
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An oxygen-assisted electron-beam-induced deposition (EBID) process, in which an oxygen flow and the vapor phase of the precursor, tetraethyl orthosilicate (TEOS), are both mixed and delivered through a single needle, is described. The optical properties of the SiO(2+δ) (- 0.04 ≤ δ ≤ +0.28) are comparable to fused silica. The electrical resistivity of both single-needle and double-needle SiO(2+δ) are comparable (greater than 7 GΩ cm) and a measured breakdown field is greater than 400 V µm(-1). Compared to the double-needle process the advantage of the single-needle technique is the ease of alignment and the proximity to the deposition location, which facilitates fabrication of complex 3D structures for nanophotonics, photovoltaics, micro- and nano-electronics applications.
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The non-trivial behaviour of phase is crucial for many important physical phenomena, such as, for example, the Aharonov-Bohm effect and the Berry phase. By manipulating the phase of light one can create 'twisted' photons, vortex knots and dislocations which has led to the emergence of the field of singular optics relying on abrupt phase changes. Here we demonstrate the feasibility of singular visible-light nano-optics which exploits the benefits of both plasmonic field enhancement and the peculiarities of the phase of light. We show that properly designed plasmonic metamaterials exhibit topologically protected zero reflection yielding to sharp phase changes nearby, which can be employed to radically improve the sensitivity of detectors based on plasmon resonances. By using reversible hydrogenation of graphene and binding of streptavidin-biotin, we demonstrate an areal mass sensitivity at a level of fg mm(-2) and detection of individual biomolecules, respectively. Our proof-of-concept results offer a route towards simple and scalable single-molecule label-free biosensing technologies.
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We present what we believe to be the first experimental study of the optical response of collective plasmon resonances in regular arrays of nanoresonators to local environment. Recently observed collective plasmon modes arise due to diffractive coupling of localized plasmons and yield almost 1 order of magnitude improvement in resonance quality. We measure the response of these modes to tiny variations of the refractive index of both gaseous and liquid media. We show that the phase sensitivity of the collective resonances can be more than 2 orders of magnitude better than the best amplitude sensitivity of the same nanodot array as well as 1 order of magnitude better than the phase sensitivity in surface plasmon resonance sensors.
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Ouro/química , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Nanotecnologia/instrumentação , Ressonância de Plasmônio de Superfície/instrumentação , Transdutores , Desenho Assistido por Computador , Desenho de Equipamento , Análise de Falha de Equipamento , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Label-free plasmonic biosensors rely either on surface plasmon polaritons or on localized surface plasmons on continuous or nanostructured noble-metal surfaces to detect molecular-binding events. Despite undisputed advantages, including spectral tunability, strong enhancement of the local electric field and much better adaptability to modern nanobiotechnology architectures, localized plasmons demonstrate orders of magnitude lower sensitivity compared with their guided counterparts. Here, we demonstrate an improvement in biosensing technology using a plasmonic metamaterial that is capable of supporting a guided mode in a porous nanorod layer. Benefiting from a substantial overlap between the probing field and the active biological substance incorporated between the nanorods and a strong plasmon-mediated energy confinement inside the layer, this metamaterial provides an enhanced sensitivity to refractive-index variations of the medium between the rods (more than 30,000 nm per refractive-index unit). We demonstrate the feasibility of our approach using a standard streptavidin-biotin affinity model and record considerable improvement in the detection limit of small analytes compared with conventional label-free plasmonic devices.
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Nanotubos/química , Ressonância de Plasmônio de Superfície/métodos , Sítios de Ligação , Biotina/química , Biotina/metabolismo , Teste de Materiais , Microscopia Eletrônica de Varredura , Tamanho da Partícula , Estreptavidina/químicaRESUMO
This work is related to the development of phase-sensitive methodologies in Surface Plasmon Resonance (SPR) biosensing. We take advantage of a specific angular dependence of phase of light, reflected under SPR geometry, on parameters of the SPR-supporting metal, and propose a polarimetry-based methodology to easily determine the optimal calibration zero point, corresponding to the maximal phase sensitivity. The proposed methodology can significantly facilitate the calibration of the system in field and multi-channel sensing, broaden the dynamic range, as well as contribute to the development of feedback loops.
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Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Desenho Assistido por Computador , Metais/química , Ressonância de Plasmônio de Superfície/instrumentação , Ressonância de Plasmônio de Superfície/métodos , Técnicas Biossensoriais/normas , Calibragem , Desenho de Equipamento , Análise de Falha de Equipamento , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Ressonância de Plasmônio de Superfície/normasRESUMO
A novel polarimetry methodology for phase-sensitive measurements in single reflection geometry is proposed for applications in optical transduction-based biological sensing. The methodology uses altering step-like chopper-based mechanical phase modulation for orthogonal s- and p- polarizations of light reflected from the sensing interface and the extraction of phase information at different harmonics of the modulation. We show that even under a relatively simple experimental arrangement, the methodology provides the resolution of phase measurements as low as 0.007 deg. We also examine the proposed approach using Total Internal Reflection (TIR) and Surface Plasmon Resonance (SPR) geometries. For TIR geometry, the response appears to be strongly dependent on the prism material with the best values for high refractive index Si. The detection limit for Si-based TIR is estimated as 10(-5) in terms Refractive Index Units (RIU) change. SPR geometry offers much stronger phase response due to a much sharper phase characteristics. With the detection limit of 3.2*10(-7) RIU, the proposed methodology provides one of best sensitivities for phase-sensitive SPR devices. Advantages of the proposed method include high sensitivity, simplicity of experimental setup and noise immunity as a result of a high stability modulation.
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Técnicas Biossensoriais/instrumentação , Óptica e Fotônica , Silício/química , Algoritmos , Fenômenos Biofísicos , Técnicas Biossensoriais/métodos , Simulação por Computador , Desenho de Equipamento , Modelos Estatísticos , Modelos Teóricos , Fótons , Refratometria , Ressonância de Plasmônio de Superfície/métodosRESUMO
A concept of phase-sensitive Si-based Total Internal Reflection bio- and chemical sensor is presented. The sensor uses the reflection of light from an internal edge of a Si prism, which is in contact with analyte material changing its index of refraction (thickness). Changes of the refractive index are monitored by measuring the differential phase shift between p- and s-polarized components of light reflected from the system. We show that due to a high refractive index of Si, such methodology leads to a high sensitivity and dynamic range of measurements. Furthermore, the Si-based platform offers an easy bioimmobilization step and excellent opportunities for the development of multi-channel microsensors taking advantage of the advanced state of development of Si-based microfabrication technologies.
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A technique of phase-polarisation contrast (PPC) for the enhancement of the contrast of a surface plasmon resonance (SPR) intensity profile is proposed and experimentally realised. The technique exploits the peculiarities of light phase and polarisation behaviour under SPR. It applies to non-optimum SPR coupling conditions and enables one to lower the resonant minimum of reflected intensity nearly to zero, and hence to increase substantially the ratio of the intensity from the resonance to that at the minimum. We observed the contrast enhancement by more than one order of magnitude when we applied the PPC scheme. The PPC can be efficiently employed in commercial SPR sensors, as it significantly reduces restrictions on allowable parameters of SPR-supporting metal films and biomolecular layers immobilised on them, facilitates SPR observation, and increases the accuracy of SPR shift measurements.