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1.
J Med Chem ; 66(21): 14669-14682, 2023 11 09.
Artículo en Inglés | MEDLINE | ID: mdl-37855413

RESUMEN

The leakage of gadolinium ions (Gd3+) from commercial Gd3+-based contrast agents (GBCAs) in patients is currently the major safety concern in clinical magnetic resonance imaging (MRI) scans, and the lack of task-specific GBCAs limits its usage in the early detection of disease and imaging of specific biological regions. Herein, ultrastable GBCAs were constructed via decorating chiral Gd-DOTA with a phenylic analogue to one of the pendent arms, and the stability constant was determined as high as 27.08, accompanied by negligible decomplexation in 1 M of HCl over 2 years. A hepatic-specific chiral Gd-DOTA was screened out as a potential alternative to commercial Gd-EOB-DTPA, while combination with functional molecules favored chiral Gd-DOTA as tumor targeting probes. Therefore, the novel chiral Gd-DOTA is believed to be an ideal platform for designing the next generation of GBCAs for various clinical purposes due to its outstanding inert nature.


Asunto(s)
Neoplasias Hepáticas , Compuestos Organometálicos , Humanos , Medios de Contraste , Imagen por Resonancia Magnética/métodos , Neoplasias Hepáticas/patología
2.
Artículo en Inglés | MEDLINE | ID: mdl-35822699

RESUMEN

The development of nanotheranostics for precision imaging-guided regulated cell death-mediated synergistic tumor therapy is still challenging. Herein, a novel multifunctional nanotheranostic agent, iRGD-coated maleimide-poly(ethylene glycol)-poly(lactic acid/glycolic acid)-encapsulated hydrophobic gold nanocages (AuNCs) and hydrophilic epigallocatechin gallate (EGCG) (PAuE) is developed for multispectral optoacoustic tomography (MSOT)-guided photothermal therapy (PTT) and chemotherapy. The portions of necroptotic and apoptotic tumor cells were 52.9 and 5.4%, respectively, at 6 h post-incubation after the AuNC-induced mild PTT treatment, whereas they became 14.0 and 46.1% after 24 h, suggesting that the switch of the cell death pathway is a time-dependent process. Mild PTT facilitated the release of EGCG which induces the downregulation of hypoxia-inducible factor-1 (HIF-1α) expression to enhance apoptosis at a later stage, realizing a remarkable tumor growth inhibition in vivo. Moreover, RNA sequence analyses provided insights into the significant changes in genes related to the cross-talk between necroptosis and apoptosis pathways via PAuE upon laser irradiation. In addition, the biodistribution and metabolic pathways of PAuE have been successfully revealed by 3D MSOT. Taken together, this strategy of first combination of EGCG and AuNC-based photothermal agent via triggering necroptosis/apoptosis to downregulate HIF-1α expression in a tumor environment provides a new insight into anti-cancer therapy.

3.
J Biomed Nanotechnol ; 17(11): 2186-2197, 2021 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-34906279

RESUMEN

Hypoxia is an important phenomenon due to insufficient oxygen supply in tumor tissue, and nitroreductase (NTR) is a characteristic enzyme used for evaluating hypoxia level in tumors. In this work, we designed a smart gold nanoparticle (AuNPs), modified by 16-mercaptoundecanoic acid (MHDA) and hypoxia-responsive 11-(2-nitro-1H-imidazol-1-yl)undecane-1-thiol (NI) ligand, that responds to the hypoxic environment in tumor sites. With proper surface ligand composition, the responsive nanoprobe exhibited aggregation through the bioreduction of the nitro group on NI ligands under hypoxic conditions and the UV-vis absorption peak maximum would shift to 630 nm from 530 nm, which acts as an "off-on" contrast agent for tumor hypoxic photoacoustic (PA) imaging. In vitro and in vivo experiments revealed that AuNPs@MHDA/NO2 exhibited an enhanced PA signal in hypoxic conditions. This study demonstrates the potential of hypoxia-responsive AuNPs as novel and sensitive diagnostic agents, which lays a firm foundation for precise cancer treatment in the future.


Asunto(s)
Nanopartículas del Metal , Técnicas Fotoacústicas , Oro , Nitrorreductasas , Hipoxia Tumoral
4.
Biomed Opt Express ; 12(6): 3597-3606, 2021 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-34221681

RESUMEN

Corneal neovascularization (CNV) compromises corneal avascularity and visual acuity. Current clinical visualization approaches are subjective and unable to provide molecular information. Photoacoustic (PA) imaging offers an objective and non-invasive way for angiogenesis investigation through hemodynamic and oxygen saturation level (sO2) quantification. Here, we demonstrate the utility of PA and slit lamp microscope for in vivo rat CNV model. PA images revealed untreated corneas exhibited higher sO2 level than treatment groups. The PA results complement with the color image obtained with slit lamp. These data suggest PA could offer an objective and non-invasive method for monitoring CNV progression and treatment outcome through the sO2 quantification.

5.
Adv Sci (Weinh) ; 8(2): 2003041, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33511018

RESUMEN

Metal phosphorous trichalcogenides (MPX3) are novel 2D nanomaterials that have recently been exploited as efficient photothermal-chemodynamic agents for cancer therapy. As a representative MPX3, FePSe3 has the potential to be developed as magnetic resonance imaging (MRI) and photoacoustic imaging (PAI) agents due to the composition of Fe and the previously revealed PA signal. Here, a FePSe3-based theranostic agent, FePSe3@APP@CCM, loaded with anti-PD-1 peptide (APP) as the inner component and CT26 cancer cell membrane (CCM) as the outer shell is reported, which acts as a multifunctional agent for MR and PA imaging and photothermal and immunotherapy against cancer. FePSe3@APP@CCM induces highly efficient tumor ablation and suppresses tumor growth by photothermal therapy under near-infrared laser excitation, which further activates immune responses. Moreover, APP blocks the PD-1/PD-L1 pathway to activate cytotoxic T cells, causing strong anticancer immunity. The combined therapy significantly prolongs the lifespan of experimental mice. The multimodal imaging and synergistic therapeutic effects of PTT and its triggered immune responses and APP-related immunotherapy are clearly demonstrated by in vitro and in vivo experiments. This work demonstrates the potential of MPX3-based biomaterials as novel theranostic agents.

6.
ACS Appl Bio Mater ; 4(5): 4152-4164, 2021 05 17.
Artículo en Inglés | MEDLINE | ID: mdl-35006828

RESUMEN

The most advantageous and attractive property of photoacoustic imaging is its capability to visualize and differentiate multiple species according to their unique absorbance profiles simultaneously in a single mixture. We here report the pH-sensitive near-infrared (NIR) croconaine (Croc) dyes-loaded copolymeric PEG-PLGA nanoparticles (NPs) for in vivo multiplexed PA imaging and pH-responsive photothermal therapy (PTT) in an orthotopic xenograft model. PEG chains on the polymeric NPs shell were conjugated with iRGD in another set of NPs to realize efficient tumor targeting. The distribution and the intensity of two sets of iRGD-targeted and nontargeted NPs inside tumors are simultaneously imaged and monitored in vivo. Meanwhile, the utilization of iRGD-targeted PPC815 NPs as a pH-active photothermal agent with promising tumor-inhibition efficacy was demonstrated. As a result, this nanoplatform is capable of assisting multiwavelength unmixing of PA imaging as well as providing remarkable photothermal ablation for anticancer treatment.


Asunto(s)
Antineoplásicos/farmacología , Materiales Biocompatibles/farmacología , Nanopartículas/química , Técnicas Fotoacústicas , Terapia Fototérmica , Polietilenglicoles/farmacología , Poliglactina 910/farmacología , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Materiales Biocompatibles/síntesis química , Materiales Biocompatibles/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Concentración de Iones de Hidrógeno , Neoplasias Mamarias Experimentales/diagnóstico por imagen , Neoplasias Mamarias Experimentales/tratamiento farmacológico , Neoplasias Mamarias Experimentales/metabolismo , Ensayo de Materiales , Ratones , Imagen Óptica , Tamaño de la Partícula , Polietilenglicoles/química , Poliglactina 910/química
7.
Int J Nanomedicine ; 15: 10271-10284, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33364758

RESUMEN

INTRODUCTION: Cancer theragnosis involving cancer diagnosis and targeted therapy simultaneously in one integrated system would be a promising solution of cancer treatment. Herein, a convenient and practical cancer theragnosis agent was constructed by combining gold nanocages (AuNCs) covered with selenium and a chitosan (CS) shell (AuNCs/Se) to incorporate the anti-cancer drug doxorubicin (DOX) as a multifunctional targeting nanocomposite (AuNCs/DOX@Se-iRGD) for photoacoustic imaging (PAI)-guided chemo-photothermal synergistic therapy that contributes to enhanced anti-cancer efficacy. The novel design of AuNCs/DOX@Se-iRGD gives the nanocomposite two outstanding properties: (1) AuNCs, with excellent LSPR property in the NIR region, act as a contrast agent for enhanced PAI and photothermal therapy (PTT); (2) Se acts as an anti-cancer nanoagent and drug delivery cargo. METHODS: The photothermal performance of these nanocomposites was evaluated in different concentrations with laser powder densities. These nanocomposites were also incubated in pH 5.3, 6.5, 7.4 PBS and NIR laser to study their drug release ability. The cellular uptake was studied by measuring the Se and Au concentrations inside the cells using inductively coupled plasma-mass spectrometry (ICP-MS). Besides, in vitro and in vivo anti-tumor activity were carried out by cytotoxicity assay MTT and tumor model nude mice, respectively. As for imaging, the PA value and images of these nanocomposites accumulated in the tumor site were sequentially collected at specific time points for 48 h. RESULTS AND DISCUSSION: The prepared AuNCs/DOX@Se-iRGD showed excellent biocompatibility and physiological stability in different media. In vivo results indicated that the targeting nanocomposite presented the strongest contrast-enhanced PAI signals, which could provide contour and location information of tumor, 24 h after intravenous injection. Likewise, the combined treatment of chemo- and photothermal synergistic therapy significantly inhibited tumor growth when compared with the two treatments carried out separately and showed negligible acute toxicity to the major organs. CONCLUSION: This study demonstrates that AuNCs/DOX@Se-iRGD has great prospect to become a multifunctional anti-tumor nanosystem for PAI-guided chemo- and photothermal synergistic therapy.


Asunto(s)
Portadores de Fármacos/química , Oro/química , Técnicas Fotoacústicas , Terapia Fototérmica/métodos , Selenio/química , Nanomedicina Teranóstica/métodos , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Terapia Combinada , Doxorrubicina/química , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Liberación de Fármacos , Humanos , Ratones , Ratones Desnudos
8.
Chem Sci ; 10(17): 4550-4559, 2019 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-31123564

RESUMEN

A cyclen backbone was utilized to study the effect of backbone rigidity on Eu(iii) luminescence sensitization using a 1,2-HOPO derivative and 2-thenoyltrifluoroacetonate (TTA) as chromophores. The restriction of molecular movement of Eu-Cy-HOPO brought about by the increased rigidity provided a tightly packed coordination environment for the octadentate Eu(iii) center which resulted in the highest overall quantum yield (30.2%) and sensitization efficiency (64.6%) among 1,2-HOPO sensitized Eu(iii) complexes. Eu-Cy-HOPO is also the first 1,2-HOPO-based lanthanide complex to emit Eu(iii) luminescence under two-photon excitation.

9.
Nanoscale Adv ; 1(2): 554-564, 2019 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-36132235

RESUMEN

The acidic microenvironment of tumor tissues has been proven to be a major characteristic for differentiation from normal tissues, thereby providing a desirable target for both disease diagnosis and functional imaging. We herein introduce a way to endow gold nanoparticles with aggregation behaviour induced by pH tuning. The nanoparticle surface was modified with two thiol conjugate molecules, which could smartly stabilize it at the pH of blood and normal tissues but induce aggregation in response to the acidic extracellular pH in tumor. The surface conjugate molecule composition effect was studied systematically, and at the optimal surface conjugate molecule composition, a pH-responsive active tumor-targeting c(RGDyk)-MHDA/LSC@AuNP nanoprobe was successfully obtained and showed a significantly enhanced contrast effect for both in vitro and in vivo photoacoustic (PA) imaging. Intravenous administration of our nanoprobe to U87MG tumor-bearing nude mice showed PA imaging contrasts almost 3-fold higher than those for the blocking group. Quantitative biodistribution data revealed that 9.7 µg g-1 of nanoprobe accumulated in the U87MG tumor 4 h post-injection. These findings might provide an effective strategy for developing new classes of intelligent and biocompatible contrast agents with a high efficiency for PA imaging and PA imaging-guided cancer therapy.

10.
Mol Imaging Biol ; 20(6): 919-929, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-29736563

RESUMEN

PURPOSE: Tumor proteases have been recognized as significant regulators in the tumor microenvironment, but the current strategies for in vivo protease imaging have tended to focus on the development of a probe design rather than the investigation of a novel imaging strategy by leveraging the imaging technique and probe. Herein, it is the first report to investigate the ability of multispectral photoacoustic imaging (PAI) to estimate the distribution of protease cleavage sites inside living tumor tissue by using an activatable photoacoustic (PA) probe. PROCEDURES: The protease MMP-2 is selected as the target. In this probe, gold nanocages (GNCs) with an absorption peak at ~ 800 nm and fluorescent dye molecules with an absorption peak at ~ 680 nm are conjugated via a specific enzymatic peptide substrate. Upon enzymatic activation by MMP-2, the peptide substrate is cleaved and the chromophores are released. Due to the different retention speeds of large GNCs and small dye molecules, the probe alters its intrinsic absorption profile and produces a distinct change in the PA signal. A multispectral PAI technique that can distinguish different chromophores based on intrinsic PA spectral signatures is applied to estimate the signal composition changes and indicate the cleavage interaction sites. Finally, the multispectral PAI technique with the activatable probe is tested in solution, cultured cells, and a subcutaneous tumor model in vivo. RESULTS: Our experiment in solution with enzyme ± inhibitor, cell culture ± inhibitor, and in vivo tumor model with administration of the developed probe ± inhibitor demonstrated the probe was cleaved by the targeted enzyme. Particularly, the in vivo estimation of the cleavage site distribution was validated with the result of ex vivo immunohistochemistry analysis. CONCLUSIONS: This novel synergy of the multispectral PAI technique and the activatable probe is a potential strategy for the distribution estimation of tumor protease activity in vivo.


Asunto(s)
Oro/química , Imagen Molecular/métodos , Sondas Moleculares/química , Neoplasias/diagnóstico , Péptido Hidrolasas/metabolismo , Técnicas Fotoacústicas/métodos , Animales , Humanos , Ratones , Ratones Desnudos , Nanocápsulas/química , Neoplasias/enzimología , Neoplasias/patología , Péptido Hidrolasas/análisis , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
11.
Chempluschem ; 82(5): 802-809, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-31961525

RESUMEN

A smart gold nanoparticle based aptasensor is developed for the sensing of this biomarker in a convenient and fast manner. A comprehensive study was performed to elucidate the driving force of DNA adsorption, different factors' effects, such as gold nanoparticle size, DNA length, concentration, and working pH towards spermine sensing by using UV/Vis absorption spectroscopy and isothermal titration calorimetry. It was found that the developed aptasensor could detect spermine by two different sensing mechanisms simply by adjusting the DNA concentration without complicated procedures. Good performance in complicated matrices was proven by the satisfactory results obtained in the spike analysis of both artificial urine and clinical urine samples. Such a flexible and smart approach described here would provide a useful tool for the fast sensing of spermine and prostate cancer screening.

12.
Int J Cancer ; 136(4): E107-16, 2015 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-25155456

RESUMEN

Metastasis accounts for the vast majority of cancer deaths. To minimize metastasis-associated mortality, it is crucially important to evaluate the metastatic potential (M.P.), that is, defined as a tendency of a primary tumor to colonize a distant organ. Dysregulated pH in solid tumors, especially the acidification of extracellular pH (pHe ) promotes dormant metastasis by driving protease-mediated digestion, disrupting cell-matrix interaction and increasing migration of cancer cells. Therefore, imaging intratumoral acidosis creates a unique opportunity to evaluate the M.P. In this work, a novel pH activatable probe was developed, in which two near-infrared (NIR) fluorophores were conjugated via a flexible and acid liable linkage. While the fluorescence of this probe is quenched due to intramolecular dimeric aggregate under neutral environment, the cleavage of pH liable linkage with the concomitant disruption of aggregates in acidic tumor microenvironment results in a remarkable fluorescence enhancement. This probe not only visualized the primary tumors with high target to background (T/B) signal ratio in vivo, but also revealed the correlation between the M.P. and acidosis distribution pattern in tumor. While the acidosis locate dispersedly at tumor periphery in highly metastatic tumor, it distribute more widely in lowly metastatic tumor and the acidification degree increases substantially from the margin to core areas. This pH activatable NIR fluorescent probe holds the potential to evaluate the M.P., monitor the therapeutic response and predict the prognosis by delineating acidosis in tumors.


Asunto(s)
Colorantes Fluorescentes , Hidrazonas , Indoles , Neoplasias Hepáticas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Acidosis/diagnóstico , Animales , Supervivencia Celular/efectos de los fármacos , Colorantes Fluorescentes/toxicidad , Células Hep G2 , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/fisiología , Humanos , Hidrazonas/toxicidad , Concentración de Iones de Hidrógeno , Indoles/toxicidad , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundario , Masculino , Ratones Desnudos , Trasplante de Neoplasias , Imagen Óptica , Espectroscopía Infrarroja Corta , Microambiente Tumoral
13.
Dalton Trans ; 43(14): 5535-45, 2014 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-24535647

RESUMEN

A series of new upconversion nanoparticles have been functionalised with tumour-targeting molecules and metal chelates, prepared following standard peptidic and thiol chemistry. The targeting strategy has been delivered via the αvß3 integrin, which is a heterodimeric cell surface receptor that is up-regulated in a variety of cancers, such as melanoma and breast cancer. The well-known DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) motif allows coordination to the radionuclide (68)Ga. Radiolabelling experiments were optimised under relatively mild conditions, and are rare amongst nanoparticulate materials. In vivo application of these probes in mouse tumour models revealed their potential as specific cancer contrast agents for PET imaging.


Asunto(s)
Medios de Contraste/farmacocinética , Nanopartículas , Animales , Línea Celular Tumoral , Medios de Contraste/química , Radioisótopos de Galio/sangre , Radioisótopos de Galio/química , Radioisótopos de Galio/farmacocinética , Compuestos Heterocíclicos con 1 Anillo/química , Humanos , Integrina alfaVbeta3/química , Melanoma/metabolismo , Ratones , Microscopía Electrónica de Transmisión , Nanopartículas/administración & dosificación , Nanopartículas/química , Nanopartículas/ultraestructura , Oligopéptidos/metabolismo , Péptidos Cíclicos/metabolismo , Tomografía de Emisión de Positrones , Radiofármacos
14.
J Biomed Nanotechnol ; 9(8): 1362-9, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23926802

RESUMEN

Gold nanoparticles have been widely explored as cancer therapeutics and diagnostic agents in recent years. With their unique subcellular size and good biocompatibility, gold nanoparticles are a promising drug delivery vehicle. In this study, folic acid-coated gold nanoparticles conjugated with fluorophore FITC through amine terminated poly(ethylene glycol) were prepared and confocal microscopy together with bright-field differential interference contrast imaging data showed that folic acid-coated gold nanoparticles accumulated mainly in cytoplasm of primary human fibroblasts, without causing any observable cytotoxicity upon exposure for 48 hours. Through the further development of a drug delivery system that conjugates doxorubicin onto the surface of gold nanoparticles with a poly(ethylene glycol) spacer via an SMCC linker, we demonstrated that multidrug resistance in cancer cells can be significantly overcome by a combination of highly efficient cellular entry and enhanced cytotoxicity of Au-SMCC-DOX nanoconjugates, as revealed both by confocal microscopy imaging and cytotoxicity assay. The prepared Au-SMCC-DOX nanoconjugates demonstrated enhanced drug accumulation and retention in multidrug resistant hepG2-R cancer cells when it was compared with free doxorubicin, with a cytoplasm accumulation profile. The results indicated that gold nanoparticles are a kind of promising drug delivery vehicle with good biocompatibility and suitable for further applications in drug delivery for improved chemotherapy, especially for overcoming multidrug resistance.


Asunto(s)
Materiales Biocompatibles Revestidos , Sistemas de Liberación de Medicamentos , Oro/química , Nanopartículas del Metal/uso terapéutico , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Antineoplásicos/farmacocinética , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/uso terapéutico , Doxorrubicina/administración & dosificación , Doxorrubicina/química , Doxorrubicina/farmacocinética , Portadores de Fármacos/síntesis química , Portadores de Fármacos/química , Portadores de Fármacos/uso terapéutico , Evaluación Preclínica de Medicamentos , Resistencia a Antineoplásicos/efectos de los fármacos , Células Hep G2 , Humanos , Ensayo de Materiales , Nanopartículas del Metal/química , Modelos Biológicos , Nanoconjugados/administración & dosificación , Nanoconjugados/química , Polietilenglicoles/administración & dosificación , Polietilenglicoles/química , Propiedades de Superficie
15.
Adv Healthc Mater ; 2(11): 1501-12, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23630101

RESUMEN

Glioblastoma multiforme (GBM) is the most common and malignant form of primary brain tumors in human. Small molecular magnetic resonance imaging (MRI) contrast agents are used for GBM diagnosis. However, conventional contrast agents have several limitations, such as low T1 relaxivity, short circulation half lives and absence of tumor targeting. Herein, we develop an upconversion nanoprobe labeled with Gd(3+) -DOTA and RGD (UCNP-Gd-RGD) for dual-modality imaging of glioblastoma. The preparation of UCNP-Gd-RGD starts with amine-functional upconversion nanoparticle core, followed by PEGylation, Gd(3+) DOTA conjugation and RGD labeling. The obtained UCNP-Gd-RGD has improved colloidal stability and reduced cytotoxicity compared with the UCNP core counterpart. Meanwhile, UCNP-Gd-RGD shows strong upconversion luminescence in deep-red region and three times enhancement of T1 relaxivity over Gd(3+) DOTA. Due to the recognition between UCNP-Gd-RGD and integrin αv ß3 receptors, the nanoprobe specifically binds to U87MG cells, as evidenced by confocal microscopy and quantified by ICP-MS. Furthermore, UCNP-Gd-RGD demonstrates a preferential retention in subcutaneous U87MG tumor xenograft as shown in both in vivo upconversion fluorescence/MR imaging studies and ex vivo analysis. UCNP-Gd-RGD, conjugated with numerous RGD peptide and T1 contrast enhancing molecules, is promising for MR imaging of glioblastoma and delineating the tumor boundary before surgery. In addition, NIR-to-red upconversion characteristic of UCNP-Gd-RGD facilitates its potential intra-operative use for fluorescence-guided tumor resection.


Asunto(s)
Neoplasias Encefálicas/diagnóstico , Compuestos Heterocíclicos , Imagen Multimodal , Nanopartículas/química , Oligopéptidos , Compuestos Organometálicos , Ensayos Antitumor por Modelo de Xenoinjerto , Animales , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Endocitosis/efectos de los fármacos , Compuestos Heterocíclicos/química , Humanos , Fenómenos Magnéticos , Imagen por Resonancia Magnética , Ratones Endogámicos BALB C , Ratones Desnudos , Nanopartículas/ultraestructura , Compuestos Organometálicos/química , Espectrofotometría Atómica , Propiedades de Superficie
16.
Nanomedicine ; 8(2): 204-11, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21704592

RESUMEN

Multidrug resistance (MDR) is a major clinical obstacle to the success of cancer chemotherapy. Here we developed a gold-doxorubicin (DOX) nanoconjugates system to overcome MDR. Gold nanoparticles (AuNPs) were first PEGylated as Au-PEG-NH(2), and DOX was then grafted onto AuNPs via a cleavable disulfide linkage (Au-PEG-SS-DOX). Confocal images revealed that the extent of intracellular uptake of Au-PEG-SS-DOX was greater than that of free DOX in the MDR cells, and inductively coupled plasma mass spectroscopy analysis further confirmed that AuNPs significantly increased the level of drug accumulation in MDR cells at a nanoparticles dose greater than 15 µM. The cytotoxicity study demonstrated that the Au-PEG-SS-DOX nanoconjugates system efficiently released the anticancer drug DOX and enhanced its cytotoxicity against MDR cancer cells. This study highlights the potential of using AuNPs for overcoming of MDR in cancer chemotherapy. FROM THE CLINICAL EDITOR: This study demonstrates that gold nanoparticles can be successfully applied to overcome MDR in cancer chemotherapy.


Asunto(s)
Doxorrubicina/farmacología , Portadores de Fármacos/química , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Oro/química , Nanopartículas del Metal/química , Doxorrubicina/química , Portadores de Fármacos/efectos adversos , Oro/efectos adversos , Células Hep G2 , Humanos , Nanopartículas del Metal/efectos adversos , Microscopía Confocal , Estructura Molecular , Polietilenglicoles/química
17.
Int J Nanomedicine ; 6: 2889-98, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-22131835

RESUMEN

Single-walled carbon nanotubes (SWNTs) have been identified as an efficient drug carrier. Here a controlled drug-delivery system based on SWNTs coated with doxorubicin (DOX) through hydrazone bonds was developed, because the hydrazone bond is more sensitive to tumor microenvironments than other covalent linkers. The SWNTs were firstly stabilized with polyethylene glycol (H(2)N-PEG-NH(2)). Hydrazinobenzoic acid (HBA) was then covalently attached on SWNTs via carbodiimide-activated coupling reaction to form hydrazine-modified SWNTs. The anticancer drug DOX was conjugated to the HBA segments of SWNT using hydrazine as the linker. The resulting hydrazone bonds formed between the DOX molecules and the HBA segments of SWNTs are acid cleavable, thereby providing a strong pH-responsive drug release, which may facilitate effective DOX release near the acidic tumor microenvironment and thus reduce its overall systemic toxicity. The DOX-loaded SWNTs were efficiently taken up by HepG2 tumor cells, and DOX was released intracellularly, as revealed by MTT assay and confocal microscope observations. Compared with SWNT-DOX conjugate formed by supramolecular interaction, the SWNT-HBA-DOX featured high weight loading and prolonged release of DOX, and thus improved its cytotoxicity against cancer cells. This study suggests that while SWNTs have great potential as a drug carrier, the efficient formulation strategy requires further study.


Asunto(s)
Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacología , Preparaciones de Acción Retardada/farmacocinética , Doxorrubicina/química , Doxorrubicina/farmacología , Portadores de Fármacos/química , Nanotubos de Carbono/química , Antibióticos Antineoplásicos/farmacocinética , Benzoatos/química , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/metabolismo , Supervivencia Celular/efectos de los fármacos , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacología , Doxorrubicina/farmacocinética , Células Hep G2 , Humanos , Concentración de Iones de Hidrógeno , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Polietilenglicoles/química
18.
Int J Nanomedicine ; 6: 2007-21, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21976976

RESUMEN

BACKGROUND: Carbon nanotubes have shown broad potential in biomedical applications, given their unique mechanical, optical, and chemical properties. In this pilot study, carbon nanotubes have been explored as multimodal drug delivery vectors that facilitate antiangiogenic therapy in zebrafish embryos. METHODS: Three different agents, ie, an antiangiogenic binding site (cyclic arginine-glycin-easpartic acid), an antiangiogenic drug (thalidomide), and a tracking dye (rhodamine), were conjugated onto single-walled carbon nanotubes (SWCNT). The biodistribution, efficacy, and biocompatibility of these triple functionalized SWCNT were tested in mammalian cells and validated in transparent zebrafish embryos. RESULTS: Accumulation of SWCNT-associated nanoconjugates in blastoderm cells facilitated drug delivery applications. Mammalian cell xenograft assays demonstrated that these antiangiogenic SWCNT nanoconjugates specifically inhibited ectopic angiogenesis in the engrafted zebrafish embryos. CONCLUSION: This study highlights the potential of using SWCNT for generating efficient nanotherapeutics.


Asunto(s)
Vasos Sanguíneos/efectos de los fármacos , Embrión no Mamífero/efectos de los fármacos , Nanoconjugados , Neovascularización Patológica/tratamiento farmacológico , Péptidos Cíclicos/farmacología , Talidomida/farmacología , Inhibidores de la Angiogénesis/farmacología , Animales , Blastodermo/citología , Blastodermo/efectos de los fármacos , Línea Celular Tumoral , Embrión no Mamífero/citología , Humanos , Nanoconjugados/química , Nanoconjugados/uso terapéutico , Nanotubos de Carbono/análisis , Nanotubos de Carbono/química , Rodaminas/análisis , Rodaminas/química , Distribución Tisular , Pez Cebra
19.
ACS Nano ; 5(10): 7838-47, 2011 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-21905691

RESUMEN

Lanthanide-doped upconversion nanoparticles (UCNPs) are considered promising novel near-infrared (NIR) bioimaging agents with the characteristics of high contrast and high penetration depth. However, the interactions between charged UCNPs and mammalian cells have not been thoroughly studied, and the corresponding intracellular uptake pathways remain unclear. Herein, our research work involved the use of a hydrothermal method to synthesize polyvinylpyrrolidone-coated UCNPs (UCNP-PVP), and then a ligand exchange reaction was performed on UCNP-PVP, with the help of polyethylenimine (PEI) and poly(acrylic acid) (PAA), to generate UCNP-PEI and UCNP-PAA. These polymer-coated UCNPs demonstrated good dispersibility in aqueous medium, had the same elemental composition and crystal phase, shared similar TEM and dynamic light scattering (DLS) size distribution, and exhibited similar upconversion luminescence efficiency. However, the positively charged UCNP-PEI evinced greatly enhanced cellular uptake in comparison with its neutral or negative counterparts, as shown by multiphoton confocal microscopy and inductively coupled plasma mass spectrometry (ICP-MS) measurements. Meanwhile, we found that cationic UCNP-PEI can be effectively internalized mainly through the clathrin endocytic mechanism, as revealed by colocalization, chemical, and genetic inhibitor studies. This study elucidates the role of the surface polymer coatings in governing UCNP-cell interactions, and it is the first report on the endocytic mechanism of positively charged lanthanide-doped UCNPs. Furthermore, this study provides important guidance for the development of UCNPs as specific intracellular nanoprobes, allowing us to control the UCNP-cell interactions by tuning surface properties.


Asunto(s)
Erbio/química , Fluoruros/química , Imagen Molecular/métodos , Nanopartículas/química , Polímeros/química , Polímeros/metabolismo , Iterbio/química , Itrio/química , Clorpromazina/farmacología , Clatrina/antagonistas & inhibidores , Clatrina/deficiencia , Clatrina/genética , Vesículas Cubiertas/efectos de los fármacos , Vesículas Cubiertas/metabolismo , Endocitosis/efectos de los fármacos , Endocitosis/genética , Técnicas de Silenciamiento del Gen , Células HeLa , Humanos , Ligandos , Mediciones Luminiscentes , Nanopartículas/toxicidad , Polímeros/toxicidad , Propiedades de Superficie
20.
J Nanosci Nanotechnol ; 9(3): 2066-71, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19435082

RESUMEN

The encapsulation of Pt nanoparticles into the cavities of MWNTs was prepared by pyrolysis of a mixture of Pt acetylacetonate and MWNTs under vacuum at 500 degrees C and subsequent thermal heating to form high surface area Pt nanostructure. Pat nanoparticles with an average size of 3.0 nm were found to be highly dispersed on the outside surface of the MWNTs and encapsulated in them. For comparison, Pd and Ru nanoparticles were also investigated using the same synthetic process to further explore the filling mechanism of metal nanoparticles inside carbon nanotubes. The presence of metal nanoparticles that were attached to the MWNTs was characterized by TEM, HRTEM, and FT-IR. The filling mechanism was also proposed.

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