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1.
Biosens Bioelectron ; 266: 116684, 2024 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-39216206

RESUMEN

Co-culture spheroids mimic tumor architecture more accurately than traditional 2D cell cultures, but non-invasive, long-term tracking of live cells within these 3D models remains a challenge. This study addresses this critical need by developing a novel approach for live cell imaging in U-87/HUF co-culture spheroids. We introduce water-soluble, biocompatible red carbon dots (R-CDs) exhibiting exceptional stability and brightness (21% quantum yield) specifically designed for imaging within these 3D models. Furthermore, we designed a microfluidic chip with ellipsoid-shaped microwells to efficiently generate two distinct co-culture spheroid types: direct mixing and core-shell. R-CDs enabled non-invasive tracking of U-87 cancer cell location within these 3D models demonstrating their efficacy for long-term monitoring of live cells in cancer research. This R-CD and microfluidic technology has the potential to accelerate cancer drug discovery by enabling live cell studies in 3D tumor models.


Asunto(s)
Carbono , Técnicas de Cocultivo , Esferoides Celulares , Humanos , Esferoides Celulares/patología , Carbono/química , Línea Celular Tumoral , Puntos Cuánticos/química , Neoplasias/patología , Neoplasias/diagnóstico por imagen , Técnicas Biosensibles/métodos , Técnicas Biosensibles/instrumentación , Materiales Biocompatibles/química , Técnicas Analíticas Microfluídicas/instrumentación , Dispositivos Laboratorio en un Chip , Diseño de Equipo
2.
Nanomaterials (Basel) ; 13(18)2023 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-37764594

RESUMEN

Cancer is one of the leading causes of death worldwide. Because each person's cancer may be unique, diagnosing and treating cancer is challenging. Advances in nanomedicine have made it possible to detect tumors and quickly investigate tumor cells at a cellular level in contrast to prior diagnostic techniques. Quantum dots (QDs) are functional nanoparticles reported to be useful for diagnosis. QDs are semiconducting tiny nanocrystals, 2-10 nm in diameter, with exceptional and useful optoelectronic properties that can be tailored to sensitively report on their environment. This review highlights these exceptional semiconducting QDs and their properties and synthesis methods when used in cancer diagnostics. The conjugation of reporting or binding molecules to the QD surface is discussed. This review summarizes the most recent advances in using QDs for in vitro imaging, in vivo imaging, and targeted drug delivery platforms in cancer applications.

3.
Mater Today Bio ; 17: 100455, 2022 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-36304975

RESUMEN

Bioluminescence imaging has advantages over fluorescence imaging, such as minimal photobleaching and autofluorescence, and greater signal-to-noise ratios in many complex environments. Although significant achievements have been made in luciferase engineering for generating bright and stable reporters, the full capability of luciferases for nanoparticle tracking has not been comprehensively examined. In biocatalysis, enhanced enzyme performance after immobilization on nanoparticles has been reported. Thus, we hypothesized that by assembling luciferases onto a nanoparticle, the resulting complex could lead to substantially improved imaging properties. Using a modular bioconjugation strategy, we attached NanoLuc (NLuc) or Akaluc bioluminescent proteins to a protein nanoparticle platform (E2), yielding nanoparticles NLuc-E2 and Akaluc-E2, both with diameters of ∼45 â€‹nm. Although no significant differences were observed between different conditions involving Akaluc and Akaluc-E2, free NLuc at pH 5.0 showed significantly lower emission values than free NLuc at pH 7.4. Interestingly, NLuc immobilization on E2 nanoparticles (NLuc-E2) emitted increased luminescence at pH 7.4, and at pH 5.0 showed over two orders of magnitude (>200-fold) higher luminescence (than free NLuc), expanding the potential for imaging detection using the nanoparticle even upon endocytic uptake. After uptake by macrophages, the resulting luminescence with NLuc-E2 nanoparticles was up to 7-fold higher than with free NLuc at 48 â€‹h. Cells incubated with NLuc-E2 could also be imaged using live bioluminescence microscopy. Finally, biodistribution of nanoparticles into lymph nodes was detected through imaging using NLuc-E2, but not with conventionally-labeled fluorescent E2. Our data demonstrate that NLuc-bound nanoparticles have advantageous properties that can be utilized in applications ranging from single-cell imaging to in vivo biodistribution.

4.
Spectrochim Acta A Mol Biomol Spectrosc ; 279: 121455, 2022 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-35679740

RESUMEN

Development of imaging probes for identification of tumors in the early stages of growth can significantly reduce the tumor-related health hazards and improve our capacity for treatment of cancer. In this work, three different furan and imidazole fluorescent derivatives abbreviated as Cyclo X, SAC and SNO are introduced for in vivo and in vitro imaging of cancer cells. The fluorescence quantum yield values were 0.226, 0.400 and 0.479 for Cyclo X, SAC and SNO, respectively. The excitation and emission wavelengths of maximum intensity were (360, 452), (350, 428) and (350, 432) nm for Cyclo X, SAC and SNO, respectively. The MTT reduction assay was used to estimate the cytotoxic activity of the proposed derivatives against HT-29 (cancer) and Vero (normal) cell lines. Cyclo X showed no cytotoxic effect, while SAC and SNO showed significantly higher cytotoxicity against the tested cell lines than cisplatin as a well-known anticancer drug. In vitro fluorescence microscopic images obtained using HT-29 cells showed that Cyclo X produced very bright images. The in vivo cancer cell imaging using 4T1 tumor-bearing mice revealed that Cyclo X is selectively accumulated in the tumor without distribution in the mice body organs. The spectral and structural stability, large Stokes shift, non-cytotoxicity and high level of selectivity for in vivo imaging are properties that make Cyclo X a suitable candidate to be used for long-term monitoring of cancer cells.


Asunto(s)
Antineoplásicos , Neoplasias , Animales , Cisplatino , Colorantes Fluorescentes , Furanos , Humanos , Imidazoles , Ratones , Microscopía Fluorescente , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico
5.
J Nanobiotechnology ; 20(1): 22, 2022 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-34991619

RESUMEN

BACKGROUND: Quantum dots (QDs) have been used as fluorophores in various imaging fields owing to their strong fluorescent intensity, high quantum yield (QY), and narrow emission bandwidth. However, the application of QDs to bio-imaging is limited because the QY of QDs decreases substantially during the surface modification step for bio-application. RESULTS: In this study, we fabricated alloy-typed core/shell CdSeZnS/ZnS quantum dots (alloy QDs) that showed higher quantum yield and stability during the surface modification for hydrophilization compared with conventional CdSe/CdS/ZnS multilayer quantum dots (MQDs). The structure of the alloy QDs was confirmed using time-of-flight medium-energy ion scattering spectroscopy. The alloy QDs exhibited strong fluorescence and a high QY of 98.0%. After hydrophilic surface modification, the alloy QDs exhibited a QY of 84.7%, which is 1.5 times higher than that of MQDs. The QY was 77.8% after the alloy QDs were conjugated with folic acid (FA). Alloy QDs and MQDs, after conjugation with FA, were successfully used for targeting human KB cells. The alloy QDs exhibited a stronger fluorescence signal than MQD; these signals were retained in the popliteal lymph node area for 24 h. CONCLUSION: The alloy QDs maintained a higher QY in hydrophilization for biological applications than MQDs. And also, alloy QDs showed the potential as nanoprobes for highly sensitive bioimaging analysis.


Asunto(s)
Aleaciones , Compuestos de Cadmio/química , Sistemas de Liberación de Medicamentos/métodos , Puntos Cuánticos , Sulfuros/química , Compuestos de Zinc/química , Aleaciones/química , Aleaciones/farmacocinética , Animales , Línea Celular Tumoral , Ácido Fólico , Células HeLa , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Microscopía Electrónica de Transmisión , Imagen Óptica , Puntos Cuánticos/química , Puntos Cuánticos/metabolismo , Compuestos de Selenio/química , Propiedades de Superficie
6.
Int J Mol Sci ; 22(12)2021 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-34208139

RESUMEN

Glioblastoma is the most malignant brain tumor among adults. Despite multimodality treatment, it remains incurable, mainly because of its extensive heterogeneity and infiltration in the brain parenchyma. Recent evidence indicates dysregulation of the expression of the Promyelocytic Leukemia Protein (PML) in primary Glioblastoma samples. PML is implicated in various ways in cancer biology. In the brain, PML participates in the physiological migration of the neural progenitor cells, which have been hypothesized to serve as the cell of origin of Glioblastoma. The role of PML in Glioblastoma progression has recently gained attention due to its controversial effects in overall Glioblastoma evolution. In this work, we studied the role of PML in Glioblastoma pathophysiology using the U87MG cell line. We genetically modified the cells to conditionally overexpress the PML isoform IV and we focused on its dual role in tumor growth and invasive capacity. Furthermore, we targeted a PML action mediator, the Enhancer of Zeste Homolog 2 (EZH2), via the inhibitory drug DZNeP. We present a combined in vitro-in silico approach, that utilizes both 2D and 3D cultures and cancer-predictive computational algorithms, in order to differentiate and interpret the observed biological results. Our overall findings indicate that PML regulates growth and invasion through distinct cellular mechanisms. In particular, PML overexpression suppresses cell proliferation, while it maintains the invasive capacity of the U87MG Glioblastoma cells and, upon inhibition of the PML-EZH2 pathway, the invasion is drastically eliminated. Our in silico simulations suggest that the underlying mechanism of PML-driven Glioblastoma physiology regulates invasion by differential modulation of the cell-to-cell adhesive and diffusive capacity of the cells. Elucidating further the role of PML in Glioblastoma biology could set PML as a potential molecular biomarker of the tumor progression and its mediated pathway as a therapeutic target, aiming at inhibiting cell growth and potentially clonal evolution regarding their proliferative and/or invasive phenotype within the heterogeneous tumor mass.


Asunto(s)
Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Proteína de la Leucemia Promielocítica/metabolismo , Línea Celular Tumoral , Proliferación Celular , Simulación por Computador , Humanos , Modelos Biológicos , Invasividad Neoplásica , Esferoides Celulares/patología
7.
Front Chem ; 9: 650006, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33777904

RESUMEN

The development of biological fluorescent probes is of great significance to the field of cancer bio-imaging. However, most current probes within the bulky hydrophobic group have limited application in aqueous medium and restricted imaging under physiological conditions. Herein, we proposed two efficient molecules to study their physical properties and imaging work, and the absorption and fluorescence intensity were collected with varying ions attending in aqueous medium. We enhance the water solubility through the quaternization reaction and form a balance between hydrophilic and hydrophobicity with dipyrrome-theneboron difluoride (BODIPY) fluorophore. We introduced pyridine and dimethylaminopyridine (DMAP) by quaternization and connected the BODIPY fluorophore by ethylenediamine. The final synthesized probes have achieved ideal affinity with HeLa cells (human cervical carcinoma cell line) in live-cell imaging which could be observed by Confocal Microscope. The probes also have a good affinity with subcutaneous tumor cells in mice in in vivo imaging, which may make them candidates as oncology imaging probes.

8.
J Biol Inorg Chem ; 25(8): 1139-1152, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33128617

RESUMEN

Development of biocompatible and multifunctional nanoprobes for tumor targeting, imaging, and therapy still remains a great challenge. Herein, gold nanoparticles (AuNPs) were synthesized in the cavity of horse spleen apoferritin protein (HoSAF) and protein surface was labeled with 2-amino-2-deoxy-glucose (2DG) as a cell surface glucose transport protein specific targeting probe to study the feasibility of its usage as a computer tomography (CT) contrast agent with tumor targeting capability through in vitro experiments. 2DG conjugated and gold-loaded apoferritin (Au-HoSAF-2DG) nanoparticles (NPs) showed selective targeting for human breast adenocarcinoma (MCF-7) cells when compared to normal breast (MCF-10A) cells. This AuNP-based imaging agent was found to be non-cytotoxic in a given concentration range with an apoptotic effect upon longer exposure times towards MCF-7 cells, while MCF-10A cells were affected less. This selective cell death would also be useful for further cancer treatments with the ability of X-ray attenuation in in vitro X-ray and computed tomography (CT) imaging.


Asunto(s)
Apoferritinas/química , Neoplasias de la Mama/patología , Glucosamina/química , Oro/química , Imagen Molecular/métodos , Nanoestructuras/química , Animales , Humanos , Células MCF-7 , Nanomedicina
9.
Cell Commun Signal ; 17(1): 143, 2019 11 08.
Artículo en Inglés | MEDLINE | ID: mdl-31703702

RESUMEN

BACKGROUND: Excessive TGF-ß signalling has been shown to underlie pulmonary hypertension (PAH). Human pulmonary artery smooth muscle cells (HPASMCs) can release extracellular vesicles (EVs) but their contents and significance have not yet been studied. Here, we aimed to analyse the contents and biological relevance of HPASMC-EVs and their transport to human pulmonary arterial endothelial cells (HPAECs), as well as the potential alteration of these under pathological conditions. METHODS: We used low-input RNA-Seq to analyse the RNA cargoes sorted into released HPASMC-EVs under basal conditions. We additionally analysed the effects of excessive TGF-ß signalling, using TGF-ß1 and BMP4, in the transcriptome of HPASMCs and their EVs. We then, for the first time, optimised Cre-loxP technology for its use with primary cells in vitro, directly visualising HPASMC-to-HPAEC communication and protein markers on cells taking up EVs. Furthermore we could analyse alteration of this transport with excessive TGF-ß signalling, as well as by other cytokines involved in PAH: IL-1ß, TNF-α and VEGFA. RESULTS: We were able to detect transcripts from 2417 genes in HPASMC-EVs. Surprisingly, among the 759 enriched in HPASMC-EVs compared to their donor cells, we found Zeb1 and 2 TGF-ß superfamily ligands, GDF11 and TGF-ß3. Moreover, we identified 90 genes differentially expressed in EVs from cells treated with TGF-ß1 compared to EVs in basal conditions, including a subset involved in actin and ECM remodelling, among which were bHLHE40 and palladin. Finally, using Cre-loxP technology we showed cell-to-cell transfer and translation of HPASMC-EV Cre mRNA from HPASMC to HPAECs, effectively evidencing communication via EVs. Furthermore, we found increased number of smooth-muscle actin positive cells on HPAECs that took up HPASMC-EVs. The uptake and translation of mRNA was also higher in activated HPAECs, when stimulated with TGF-ß1 or IL-1ß. CONCLUSIONS: HPASMC-EVs are enriched in RNA transcripts that encode genes that could contribute to vascular remodelling and EndoMT during development and PAH, and TGF-ß1 up-regulates some that could enhance this effects. These EVs are functionally transported, increasingly taken up by activated HPAECs and contribute to EndoMT, suggesting a potential effect of HPASMC-EVs in TGF-ß signalling and other related processes during PAH development.


Asunto(s)
Vesículas Extracelulares/metabolismo , Hipertensión Pulmonar/patología , Miocitos del Músculo Liso/patología , Arteria Pulmonar/patología , Transducción de Señal , Factor de Crecimiento Transformador beta/metabolismo , Remodelación Vascular , Proteínas Morfogenéticas Óseas/metabolismo , Endotelio Vascular/patología , Factores de Diferenciación de Crecimiento/metabolismo , Humanos , Interleucina-1beta/metabolismo , Fenotipo , Factor de Crecimiento Transformador beta3/metabolismo , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/metabolismo
10.
Malar J ; 18(1): 155, 2019 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-31046772

RESUMEN

BACKGROUND: The protective efficacy of the most promising malaria whole-parasite based vaccine candidates critically depends on the parasite's potential to migrate in the human host. Key components of the parasite motility machinery (e.g. adhesive proteins, actin/myosin-based motor, geometrical properties) have been identified, however the regulation of this machinery is an unknown process. METHODS: In vitro microscopic live imaging of parasites in different formulations was performed and analysed, with the quantitative analysis software SMOOTIn vitro, their motility; their adherence capacity, movement pattern and velocity during forward locomotion. RESULTS: SMOOTIn vitro enabled the detailed analysis of the regulation of the motility machinery of Plasmodium berghei in response to specific (macro)molecules in the formulation. Albumin acted as an essential supplement to induce parasite attachment and movement. Glucose, salts and other whole serum components further increased the attachment rate and regulated the velocity of the movement. CONCLUSIONS: Based on the findings can be concluded that a complex interplay of albumin, glucose and certain salts and amino acids regulates parasite motility. Insights in parasite motility regulation by supplements in solution potentially provide a way to optimize the whole-parasite malaria vaccine formulation.


Asunto(s)
Medios de Cultivo/química , Locomoción/efectos de los fármacos , Plasmodium berghei/efectos de los fármacos , Esporozoítos/fisiología , Albúminas/farmacología , Animales , Culicidae/parasitología , Medios de Cultivo/farmacología , Femenino , Glucosa/farmacología , Microscopía Intravital , Malaria/parasitología , Ratones , Plasmodium berghei/fisiología , Programas Informáticos
11.
Bioorg Med Chem ; 27(9): 1855-1862, 2019 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-30910476

RESUMEN

Many imaging probes have been developed for a wide variety of imaging modalities. However, no optical imaging probe could be utilized for both microscopic and whole animal imaging. To fill the gap, the dual-wavelength fluorescent imaging nanoprobe was developed to simultaneously carry both visible-range fluorescent dye and near-infrared (NIR) dye. Emission scan confirms that the nanoprobe exhibits two separate peaks with strong fluorescent intensity in both visible and NIR ranges. Furthermore, the dual-wavelength fluorescent nanoprobe has high photostability and colloidal stability, as well as long shelf-life. In vitro cell culture experiments show that the nanoprobe has the ability to label different types of cells (namely, esophageal, prostate, fibroblast and macrophage cell) for fluorescent microscope imaging. More importantly, cell tracking experiments confirm that cell migration and distribution in various organs can be tracked in real time using in vivo whole-body NIR imaging and in vitro microscopic imaging, respectively.


Asunto(s)
Rastreo Celular/métodos , Colorantes Fluorescentes/química , Nanopartículas/química , Animales , Carbocianinas/química , Línea Celular , Supervivencia Celular/efectos de los fármacos , Neoplasias Esofágicas/diagnóstico por imagen , Fluoresceína-5-Isotiocianato/química , Ratones , Microscopía Fluorescente , Nanopartículas/metabolismo , Nanopartículas/toxicidad , Distribución Tisular
12.
ACS Appl Bio Mater ; 2(10): 4634-4647, 2019 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-35021422

RESUMEN

The biomedical application of yttria (Y2O3) as a bulk material to host a series of rare earth elements (RE3+) has been explored in the current investigation. Dy3+, Gd3+, Tb3+, Yb3+, Eu3+, and Nd3+ were chosen for this purpose, and their corresponding concentrations in Y2O3 have been varied to obtain five different combinations. The results ascertain the potential of Y2O3 to host different RE3+ to retain a discrete cubic yttria (c-Y2O3) devoid of significant structural distortion until 1400 °C. Depending upon the size of RE3+, either a contracted or expanded cubic Y2O3 unit cell has been determined from the XRD and Raman analyses. Other than the typical vibrational modes of c-Y2O3, Raman spectra also unveiled characteristic emission features of RE3+ that were dependent on the excitation laser used to record the spectra. The characteristic absorption and emission characteristics depending on the type of RE3+ substitutions were determined from the optical measurements. Pore free microstructures determined from the morphological analysis are reflected in the enhanced mechanical behavior of RE3+ doped Y2O3 specimens. Dy3+ and Yb3+ substituted Y2O3 unveiled computed tomography (CT) imaging features. Dy3+, Tb3+, and Nd3+ dopant compositions delivered T2 magnetic resonance imaging (MRI) contrast features, while the specimen comprising Gd3+ revealed both T1 and T2 MRI characteristics.

13.
Magn Reson Med ; 81(5): 2937-2946, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30426563

RESUMEN

PURPOSE: The purpose of this study is to provide a standard method for flow velocity measurements with phase-contrast (PC) MRI. This method can be used for in vitro studies that place high demands on measurement accuracy. Clinically relevant PC MRI techniques can be validated using this method before being applied in vivo. METHODS: Many motion-related errors in PC MRI, particularly flow misregistration, depend on the timing of the encoding gradients in the pulse sequence. By synchronizing all encoding gradients and shortening the overall encoding interval, these errors can be significantly reduced. Based on this concept, a single-point PC MRI method is proposed. RESULTS: Flow experiments were conducted in vitro. No considerable errors were found in the velocity data of the proposed method. For comparison, a conventional PC MRI technique showed up to 100% local velocity deviation and up to 35% flow rate deviation in the same experiments. CONCLUSIONS: With the proposed method, the overall measurement accuracy is significantly increased compared to conventional PC MRI techniques. Due to long acquisition times and high specific absorption rates, this method can only be applied in vitro.


Asunto(s)
Constricción , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Diseño de Equipo , Microscopía de Contraste de Fase , Modelos Teóricos , Movimiento (Física) , Reproducibilidad de los Resultados , Reología
14.
J Fluoresc ; 28(4): 959-966, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29968047

RESUMEN

In this paper, a fast and simplest one-pot tactic was used to synthesis fluorescent oxygen doped carbon dots from Tween-20 (TTO-CDs) is reported. The TTO-CDs were microwavically synthesized by using Tween-20 as both the carbon precursor and the oxygen dopant as well. The surface morphology, crystalline and/or amorphous nature, composition and optical assets of synthesized TTO-CDs were studied by means of existing techniques. From the results, it was confirmed that the as-synthesized TTO-CDs are amorphous in nature, monodispersed, sphere-shaped and the typical particle size range is 5 ± 1.5 nm. The synthesized TTO-CDs emits strong blue fluorescence at 390 nm under excitation of 335 nm. Most interestingly, the excitation dependent emission property of synthesized TTO-CDs was exposed from fluorescence results. The synthesized TTO-CDs have quantum yield of about 14% against quinine sulfate as reference standard. The biotoxicity of synthesized TTO-CDs on HeLa cells was assessed through cytotoxicity assay. These results implied that the fluorescent TTO-CDs showed less biotoxicity, and further which was efficaciously applied as a multicolor staining and bioimaging probe for the confocal imaging of HeLa cells.


Asunto(s)
Carbono/química , Colorantes Fluorescentes/química , Microondas , Imagen Óptica , Oxígeno/química , Puntos Cuánticos/química , Supervivencia Celular , Colorantes Fluorescentes/síntesis química , Células HeLa , Humanos , Tamaño de la Partícula , Polisorbatos/química , Propiedades de Superficie , Células Tumorales Cultivadas
15.
Mater Sci Eng C Mater Biol Appl ; 86: 56-61, 2018 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-29525097

RESUMEN

Upconversion nanoparticles (UCNPs) possess a unique type of photoluminescence (PL) in which lower-energy excitation is converted into higher-energy emission via multi-photon absorption processes. In this work, we have used a facile one-step hydrothermal method promoted water solubility to synthesis NaLuGdF4:Yb3+/Er3+(Tm3+) UCNPs coated with malonic acid (MA). Scanning electron microscopy images and X-ray diffraction patterns reveal sphere-shaped UCNPs with an average size of ~80nm crystallized in the cubic NaLuF4 structure. The characteristic vibrations of cubic UCNPs have been taken into account by using Fourier-transform infrared spectroscopy. Based on PL studies, we have determined an optimal concentration of Gd3+ doping. The dependence of upconversion PL intensity on Gd3+ concentration is discussed via the results of magnetization measurements, which is related to the coupling/uncoupling of Gd3+ ions. Particularly, our study reveals that carboxyl-functionalized NaLuGdF4:Yb3+/Er3+(Tm3+) UCNPs have a relatively high cell viability with HeLa cells.


Asunto(s)
Nanopartículas del Metal/química , Supervivencia Celular/efectos de los fármacos , Erbio/química , Fluoruros/química , Gadolinio/química , Células HeLa , Humanos , Lutecio/química , Nanopartículas del Metal/toxicidad , Microscopía Electrónica de Rastreo , Microscopía Fluorescente , Tamaño de la Partícula , Sodio/química , Solubilidad , Espectroscopía Infrarroja por Transformada de Fourier , Iterbio/química
16.
IEEE Trans Radiat Plasma Med Sci ; 2(4): 300-306, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33778232

RESUMEN

Respiratory motions in small animals PET cause image degradation during reconstruction. This work aims to develop a motion compensated 4D-PET reconstruction method using accurate motion corrections and attenuation corrections from 4D-CBCT images reconstructed using a simultaneous motion estimation and image reconstruction (SMEIR) method. Projections of 4D-CBCT were calculated using a ray-tracing method on a digital 4D rat phantom, and list-mode data of 4D-PET with matched respiratory phases were simulated using the GATE Monte Carlo package. The respiratory rate was set at 1.0 second per cycle with 10 phases of 30 projection images each. 4D-CBCT images were reconstructed using the SMEIR method and motion information and linear attenuation from 4D-CBCT were subsequently used for motion compensated 4D-PET reconstruction and attenuation corrections. We quantitatively evaluate the reconstructed 4D-PET using the errors of tumor volume and standard uptake values of tumors with different sizes. The tumor motion was successfully reconstructed and showed good agreement with the original phantom. The proposed method reduced tumor volume errors and standard uptake value errors. For tumor diameters of 3.0, 4.5, and 6.0 mm, the tumor volume errors are 32.5%, 29.2% and 19.4% respectively with motion compensation and 45.1%, 37.5% and 20.2% respectively without compensation.

17.
Colloids Surf B Biointerfaces ; 159: 820-828, 2017 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-28888199

RESUMEN

Here we report the first of the phenosafranin-chlorambucil conjugate as a new type of a chemotherapeutic agent suitable for dual detection methods (spectrophotometric and fluorescence) in imaging systems and cancer treatment. The synthetic cationic dye (3,7-diamino-5-phenylphenazinium chloride) is used as a fluorescent light-triggered scaffold that acts as a carrier for an anti-cancer drug. The chlorambucil was attached covalently via amide bonds to the bifunctional fluorophore, which facilitates tracking with visible light. Our studies revealed that the new photosensitive compound exhibits improved intrinsic activity in vitro in HeLa cells culture experiments; thus it could be a potential anti-cancer candidate in theranostic drug-delivery systems. In light of the urgent need for in vivo monitoring of the biodistribution of anti-cancer drugs, this strategy for the synthesis of innovative conjugates based on the phenosafranin backbone offers a promising possibility for drug control in anti-cancer therapy and diagnosis. This aspect makes the phenosafranin-chlorambucil conjugate unique among currently available biomarkers.


Asunto(s)
Antineoplásicos/química , Clorambucilo/química , Fenazinas/química , Sistemas de Liberación de Medicamentos/métodos , Células HeLa , Humanos
18.
Biosens Bioelectron ; 79: 922-9, 2016 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-26802574

RESUMEN

Herein we report a simple and sensitive fluorescent sensing platform for phenol and enzyme activity detection based on 3-aminobenzeneboronic acid functionalized CuInS2 QDs (APBA-CuInS2 QDs). APBA were covalently linked to CuInS2 QDs surface to form the APBA-CuInS2 QDs which had a fairly symmetric fluorescence emission peak at 736 nm in the near-infrared spectral region. In the presence of tyrosinase, phenol can be catalyzed the oxidization into catechol, which could reactive toward the boronic acid functional groups of APBA-CuInS2 QDs to form five-membered cyclic esters, leading to the fluorescence quenching of the QDs. The effective fluorescence quenching of APBA-CuInS2 QDs by phenol enabled this proposed nanosensor to sensitively detect the phenol product-related enzyme system, such as acid phosphatase-catalyzed hydrolysis of phenyl phosphate. Thus, the proposed biosensor was utilized for facile, sensitive, and selective detection phenol, tyrosinase and acid phosphatase. The detection limits of phenol, tyrosinase and acid phosphatase reached 0.05 µmol L(-1), 0.03 U mL(-1) and 6 nU mL(-1) for, respectively. The feasibility of the proposed nanosensor in real samples assay was also studied and satisfactory results were obtained. Meanwhile, using the APBA-CuInS2 QDs fluorescence probe, we successfully performed in vitro imaging of human prostate cancer cells, suggesting the biocompatible sensor has potentially extensive application clinic diagnoses assays.


Asunto(s)
Colorantes Fluorescentes/química , Monofenol Monooxigenasa/análisis , Fenoles/análisis , Puntos Cuánticos/química , Técnicas Biosensibles/métodos , Ácidos Borónicos/química , Línea Celular Tumoral , Humanos , Límite de Detección , Masculino , Microscopía Fluorescente/métodos , Monofenol Monooxigenasa/metabolismo , Imagen Óptica , Fenoles/metabolismo , Neoplasias de la Próstata/enzimología , Espectrometría de Fluorescencia/métodos
19.
Acta Biomater ; 14: 208-16, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25463504

RESUMEN

Fluorescently labeled nanoparticles (NPs) are used in a wide range of biomedical and nanotoxicological studies to elucidate their interactions with cellular components and their intracellular localization. As commonly used fluorescence microscopes are usually limited in their performance to a few channels which detect the emitted fluorescence light in the red, green and blue color range, the simultaneous colocalization of accumulated fluorescent NPs with cellular markers is often difficult and remains a challenge due to spectral overlay of NP fluorescence and fluorescence of stained cellular components. To overcome this problem we have synthesized three different photostable dual-labeled fluorescent core/shell silica NPs with high fluorescence intensity and well-defined shape, size and surface chemistry. The synthesis route of dual fluorophore doped silica (DFDS) NPs was based on a water-in-oil microemulsion method and includes the separate incorporation of two fluorophores in the core or shell. The suitability of DFDS for colocalization studies was assessed and successfully demonstrated with human osteoblast cells. Parallel visualization of DFDS NPs with two separate microscope channels allowed cellular NP uptake and discrimination from fluorescently stained cellular components, even in triple stained cells that show fluorescence for the cytoskeleton protein actin (green), the nucleus (blue) and collagen (red). Our results demonstrate the feasibility and straightforwardness of the approach for colocalization studies at a single-cell level to discern clearly the accumulation of NPs from triple-stained cellular components. Such NPs with multiple fluorescence characteristics have a great potential to replace single fluorescent NPs for in vitro studies, when multiple staining of cellular components is required.


Asunto(s)
Colorantes Fluorescentes/química , Microscopía Fluorescente , Imagen Molecular/métodos , Nanopartículas/química , Osteoblastos/citología , Osteoblastos/metabolismo , Dióxido de Silicio/química , Coloración y Etiquetado , Humanos , Nanopartículas/ultraestructura , Tamaño de la Partícula
20.
Int J Nanomedicine ; 9: 1323-37, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24648731

RESUMEN

BACKGROUND: Quantum dots are fluorescent nanoparticles with unique photophysical properties that allow them to be used as diagnostic, therapeutic, and theranostic agents, particularly in medical and surgical oncology. Near-infrared-emitting quantum dots can be visualized in deep tissues because the biological window is transparent to these wavelengths. Their small sizes and free surface reactive groups that can be conjugated to biomolecules make them ideal probes for in vivo cancer localization, targeted chemotherapy, and image-guided cancer surgery. The human epidermal growth factor receptor 2 gene (HER2/neu) is overexpressed in 25%-30% of breast cancers. The current methods of detection for HER2 status, including immunohistochemistry and fluorescence in situ hybridization, are used ex vivo and cannot be used in vivo. In this paper, we demonstrate the application of near-infrared-emitting quantum dots for HER2 localization in fixed and live cancer cells as a first step prior to their in vivo application. METHODS: Near-infrared-emitting quantum dots were characterized and their in vitro toxicity was established using three cancer cell lines, ie, HepG2, SK-BR-3 (HER2-overexpressing), and MCF7 (HER2-underexpressing). Mouse antihuman anti-HER2 monoclonal antibody was conjugated to the near-infrared-emitting quantum dots. RESULTS: In vitro toxicity studies showed biocompatibility of SK-BR-3 and MCF7 cell lines with near-infrared-emitting quantum dots at a concentration of 60 µg/mL after one hour and 24 hours of exposure. Near-infrared-emitting quantum dot antiHER2-antibody bioconjugates successfully localized HER2 receptors on SK-BR-3 cells. CONCLUSION: Near-infrared-emitting quantum dot bioconjugates can be used for rapid localization of HER2 receptors and can potentially be used for targeted therapy as well as image-guided surgery.


Asunto(s)
Neoplasias/diagnóstico , Neoplasias/metabolismo , Puntos Cuánticos , Receptor ErbB-2/metabolismo , Animales , Anticuerpos Monoclonales , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Femenino , Células Hep G2 , Humanos , Células MCF-7 , Ratones , Nanomedicina , Nanotecnología , Puntos Cuánticos/química , Puntos Cuánticos/ultraestructura , Receptor ErbB-2/inmunología , Espectroscopía Infrarroja Corta
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