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1.
Circ Res ; 135(5): e114-e132, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-38989585

RESUMEN

BACKGROUND: Atherosclerosis is a chronic inflammatory disease causing a fatal plaque rupture, and its key aspect is a failure to resolve inflammation. We hypothesize that macrophage-targeted near-infrared fluorescence emitting photoactivation could simultaneously assess macrophage/lipid-rich plaques in vivo and facilitate inflammation resolution. METHODS: We fabricated a Dectin-1-targeted photoactivatable theranostic agent through the chemical conjugation of the near-infrared fluorescence-emitting photosensitizer chlorin e6 and the Dectin-1 ligand laminarin (laminarin-chlorin e6 [LAM-Ce6]). Intravascular photoactivation by a customized fiber-based diffuser after administration of LAM-Ce6 effectively reduced inflammation in the targeted plaques of atherosclerotic rabbits in vivo as serially assessed by dual-modal optical coherence tomography-near-infrared fluorescence structural-molecular catheter imaging after 4 weeks. RESULTS: The number of apoptotic macrophages peaked at 1 day after laser irradiation and then resolved until 4 weeks. Autophagy was strongly augmented 1 hour after the light therapy, with the formation of autophagolysosomes. LAM-Ce6 photoactivation increased the terminal deoxynucleotidyl transferase dUTP (deoxyuridine triphosphate) nick end labeling/RAM11 (rabbit monocyte/macrophage antibody)- and MerTK (c-Mer tyrosine kinase)-positive cells in the plaques, suggesting enhanced efferocytosis. In line with inflammation resolution, photoactivation reduced the plaque burden through fibrotic replacement via the TGF (transforming growth factor)-ß/CTGF (connective tissue growth factor) pathway. CONCLUSIONS: Optical coherence tomography-near-infrared fluorescence imaging-guided macrophage Dectin-1-targetable photoactivation could induce the transition of macrophage/lipid-rich plaques into collagen-rich lesions through autophagy-mediated inflammation resolution and TGF-ß-dependent fibrotic replacement. This novel strategy offers a new opportunity for the catheter-based theranostic strategy.


Asunto(s)
Clorofilidas , Imagen Multimodal , Fármacos Fotosensibilizantes , Placa Aterosclerótica , Porfirinas , Tomografía de Coherencia Óptica , Animales , Placa Aterosclerótica/diagnóstico por imagen , Conejos , Imagen Multimodal/métodos , Tomografía de Coherencia Óptica/métodos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Macrófagos/metabolismo , Nanomedicina Teranóstica/métodos , Ratones , Masculino , Autofagia , Tirosina Quinasa c-Mer/metabolismo , Apoptosis
2.
Chem Eng J ; 455: 140753, 2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-36506703

RESUMEN

The COVID-19 pandemic and the resulting supply chain disruption have rekindled crucial needs for safe storage and transportation of essential items. Despite recent advances, existing temperature monitoring technologies for cold chain management fall short in reliability, cost, and flexibility toward customized cold chain management for various products with different required temperature. In this work, we report a novel capsule-based colorimetric temperature monitoring system with precise and readily tunable temperature ranges. Triple emulsion drop-based microfluidic technique enables rapid production of monodisperse microcapsules with an interstitial phase-change oil (PCO) layer with precise control over its dimension and composition. Liquid-solid phase transition of the PCO layer below its freezing point triggers the release of the encapsulated payload yielding drastic change in color, allowing user-friendly visual monitoring in a highly sensitive manner. Simple tuning of the PCO layer's compositions can further broaden the temperature range in a precisely controlled manner. The proposed simple scheme can readily be formulated to detect both temperature rise in the frozen environment and freeze detection as well as multiple temperature monitoring. Combined, these results support a significant step forward for the development of customizable colorimetric monitoring of a broad range of temperatures with precision.

3.
Int J Mol Sci ; 24(21)2023 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-37958960

RESUMEN

In present study, icariin (ICA)/tannic acid (TA)-nanodiamonds (NDs) were prepared as follows. ICA was anchored to ND surfaces with absorbed TA (ICA/TA-NDs) and we evaluated their in vitro anti-inflammatory effects on lipopolysaccharide (LPS)-activated macrophages and in vivo cartilage protective effects on a rat model of monosodium iodoacetate (MIA)-induced osteoarthritis (OA). The ICA/TA-NDs showed prolonged release of ICA from the NDs for up to 28 days in a sustained manner. ICA/TA-NDs inhibited the mRNA levels of pro-inflammatory elements, including matrix metalloproteinases-3 (MMP-3), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and increased the mRNA levels of anti-inflammatory factors (i.e., IL-4 and IL-10) in LPS-activated RAW 264.7 macrophages. Animal studies exhibited that intra-articular injection of ICA/TA-NDs notably suppressed levels of IL-6, MMP-3, and TNF-α and induced level of IL-10 in serum of MIA-induced OA rat models in a dose-dependent manner. Furthermore, these noticeable anti-inflammatory effects of ICA/TA-NDs remarkably contributed to the protection of the progression of MIA-induced OA and cartilage degradation, as exhibited by micro-computed tomography (micro-CT), gross findings, and histological investigations. Accordingly, in vitro and in vivo findings suggest that the prolonged ICA delivery of ICA/TA-NDs possesses an excellent latent to improve inflammation as well as defend against cartilage disorder in OA.


Asunto(s)
Cartílago Articular , Nanodiamantes , Osteoartritis , Ratas , Animales , Interleucina-10/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Metaloproteinasa 3 de la Matriz/genética , Metaloproteinasa 3 de la Matriz/metabolismo , Interleucina-6/metabolismo , Lipopolisacáridos/farmacología , Microtomografía por Rayos X , Cartílago Articular/metabolismo , Osteoartritis/metabolismo , Antiinflamatorios/farmacología , Ácido Yodoacético/efectos adversos , ARN Mensajero/metabolismo , Modelos Animales de Enfermedad
4.
Int J Mol Sci ; 24(4)2023 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-36835253

RESUMEN

Inflammatory environments provide vital biochemical stimuli (i.e., oxidative stress, pH, and enzymes) for triggered drug delivery in a controlled manner. Inflammation alters the local pH within the affected tissues. As a result, pH-sensitive nanomaterials can be used to effectively target drugs to the site of inflammation. Herein, we designed pH-sensitive nanoparticles in which resveratrol (an anti-inflammatory and antioxidant compound (RES)) and urocanic acid (UA) were complexed with a pH-sensitive moiety using an emulsion method. These RES-UA NPs were characterized by transmission electron microscopy, dynamic light scattering, zeta potential, and FT-IR spectroscopy. The anti-inflammatory and antioxidant activities of the RES-UA NPs were assessed in RAW 264.7 macrophages. The NPs were circular in shape and ranged in size from 106 to 180 nm. The RES-UA NPs suppressed the mRNA expression of the pro-inflammatory molecules inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages in a concentration-dependent manner. Incubation of LPS-stimulated macrophages with RES-UA NPs reduced the generation of reactive oxygen species (ROS) in a concentration-dependent manner. These results suggest that pH-responsive RES-UA NPs can be used to decrease ROS generation and inflammation.


Asunto(s)
Antiinflamatorios , Antioxidantes , Nanopartículas , Resveratrol , Ácido Urocánico , Humanos , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antioxidantes/química , Antioxidantes/farmacología , Ciclooxigenasa 2/metabolismo , Concentración de Iones de Hidrógeno , Inflamación/metabolismo , Lipopolisacáridos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Resveratrol/química , Resveratrol/farmacología , Espectroscopía Infrarroja por Transformada de Fourier , Factor de Necrosis Tumoral alfa/metabolismo , Ácido Urocánico/química , Ácido Urocánico/farmacología
5.
J Nanobiotechnology ; 19(1): 338, 2021 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-34689768

RESUMEN

BACKGROUND: Photoactivation targeting macrophages has emerged as a therapeutic strategy for atherosclerosis, but limited targetable ability of photosensitizers to the lesions hinders its applications. Moreover, the molecular mechanistic insight to its phototherapeutic effects on atheroma is still lacking. Herein, we developed a macrophage targetable near-infrared fluorescence (NIRF) emitting phototheranostic agent by conjugating dextran sulfate (DS) to chlorin e6 (Ce6) and estimated its phototherapeutic feasibility in murine atheroma. Also, the phototherapeutic mechanisms of DS-Ce6 on atherosclerosis were investigated. RESULTS: The phototheranostic agent DS-Ce6 efficiently internalized into the activated macrophages and foam cells via scavenger receptor-A (SR-A) mediated endocytosis. Customized serial optical imaging-guided photoactivation of DS-Ce6 by light illumination reduced both atheroma burden and inflammation in murine models. Immuno-fluorescence and -histochemical analyses revealed that the photoactivation of DS-Ce6 produced a prominent increase in macrophage-associated apoptotic bodies 1 week after laser irradiation and induced autophagy with Mer tyrosine-protein kinase expression as early as day 1, indicative of an enhanced efferocytosis in atheroma. CONCLUSION: Imaging-guided DS-Ce6 photoactivation was able to in vivo detect inflammatory activity in atheroma as well as to simultaneously reduce both plaque burden and inflammation by harmonic contribution of apoptosis, autophagy, and lesional efferocytosis. These results suggest that macrophage targetable phototheranostic nanoagents will be a promising theranostic strategy for high-risk atheroma.


Asunto(s)
Aterosclerosis/metabolismo , Células Espumosas/metabolismo , Fármacos Fotosensibilizantes , Nanomedicina Teranóstica/métodos , Animales , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Línea Celular Tumoral , Endocitosis/efectos de los fármacos , Rayos Infrarrojos , Masculino , Ratones , Ratones Noqueados , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacocinética , Fármacos Fotosensibilizantes/farmacología , Células RAW 264.7
6.
Int J Mol Sci ; 22(9)2021 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-33924775

RESUMEN

Calcium carbonate (CaCO3)-based materials have received notable attention for biomedical applications owing to their safety and beneficial characteristics, such as pH sensitivity, carbon dioxide (CO2) gas generation, and antacid properties. Herein, to additionally incorporate antioxidant and anti-inflammatory functions, we prepared tannylated CaCO3 (TA-CaCO3) materials using a simple reaction between tannic acid (TA), calcium (Ca2+), and carbonate (CO32-) ions. TA-CaCO3 synthesized at a molar ratio of 1:75 (TA:calcium chloride (CaCl2)/sodium carbonate (Na2CO3)) showed 3-6 µm particles, comprising small nanoparticles in a size range of 17-41 nm. The TA-CaCO3 materials could efficiently neutralize the acid solution and scavenge free radicals. In addition, these materials could significantly reduce the mRNA levels of pro-inflammatory factors and intracellular reactive oxygen species, and protect chondrocytes from toxic hydrogen peroxide conditions. Thus, in addition to their antacid property, the prepared TA-CaCO3 materials exert excellent antioxidant and anti-inflammatory effects through the introduction of TA molecules. Therefore, TA-CaCO3 materials can potentially be used to treat inflammatory cells or diseases.


Asunto(s)
Antiinflamatorios/química , Antioxidantes/química , Carbonato de Calcio/química , Taninos/química , Antiácidos/química , Antiácidos/farmacología , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Células Cultivadas , Condrocitos/efectos de los fármacos , Sistemas de Liberación de Medicamentos , Humanos
7.
Adv Exp Med Biol ; 1250: 177-188, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32601945

RESUMEN

Biphasic calcium phosphate bioceramics consist of an intimate mixture of hydroxyapatite (HA) and beta-tricalcium phosphate (ß-TCP) in varying ratios. Due to their biocompatibility, osteoconductivity, and safety in in vitro, in vivo, and clinical models, they have become promising bone substitute biomaterials and are recommended for use as alternatives for or as additives in bone tissue regeneration in various orthopedic and dental applications. Many studies have demonstrated the potential uses of BCP bioceramics as scaffolds for tissue engineering. Here, we highlight the recent advances in the uses of BCP bioceramics and functionalized BCPs for bone tissue regeneration.


Asunto(s)
Regeneración Ósea , Sustitutos de Huesos , Hidroxiapatitas , Sustitutos de Huesos/química , Sustitutos de Huesos/normas , Humanos
8.
Int J Mol Sci ; 22(1)2020 Dec 26.
Artículo en Inglés | MEDLINE | ID: mdl-33375356

RESUMEN

Macrophage-derived foam cells play critical roles in the initiation and progression of atherosclerosis. Activated macrophages and foam cells are important biomarkers for targeted imaging and inflammatory disease therapy. Macrophages also express the dectin-1 receptor, which specifically recognizes ß-glucan (Glu). Here, we prepared photoactivatable nanoagents (termed Glu/Ce6 nanocomplexes) by encapsulating hydrophobic chlorin e6 (Ce6) within the triple-helix structure of Glu in aqueous condition. Glu/Ce6 nanocomplexes generate singlet oxygen upon laser irradiation. The Glu/Ce6 nanocomplexes were internalized into foam cells and delivered Ce6 molecules into the cytoplasm of foam cells. Upon laser irradiation, they induced significant membrane damage and apoptosis of foam cells. These results suggest that Glu/Ce6 nanocomplexes can be a photoactivatable material for treating atherogenic foam cells.


Asunto(s)
Aterosclerosis/tratamiento farmacológico , Células Espumosas/efectos de los fármacos , Glucanos/farmacología , Rayos Láser , Nanopartículas/administración & dosificación , Porfirinas/farmacología , Fármacos Sensibilizantes a Radiaciones/farmacología , Animales , Apoptosis , Aterosclerosis/metabolismo , Aterosclerosis/patología , Clorofilidas , Células Espumosas/metabolismo , Células Espumosas/patología , Glucanos/administración & dosificación , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/patología , Ratones , Nanopartículas/química , Fotoquimioterapia , Porfirinas/administración & dosificación , Fármacos Sensibilizantes a Radiaciones/administración & dosificación , Oxígeno Singlete/química , Oxígeno Singlete/metabolismo
9.
Int J Mol Sci ; 19(11)2018 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-30445673

RESUMEN

In this study, a novel three-dimensional (3D) bone morphogenic protein-2 (BMP-2)-delivering tannylated polycaprolactone (PCL) (BMP-2/tannic acid (TA)/PCL) scaffold with anti-oxidant, anti-inflammatory, and osteogenic activities was fabricated via simple surface coating with TA, followed by the immobilization of BMP-2 on the TA-coated PCL scaffold. The BMP-2/TA/PCL scaffold showed controlled and sustained BMP-2 release. It effectively scavenged reactive oxygen species (ROS) in cells, and increased the proliferation of MC3T3-E1 cells pre-treated with hydrogen peroxide (H2O2). Additionally, the BMP-2/TA/PCL scaffold significantly suppressed the mRNA levels of pro-inflammatory cytokines, including matrix metalloproteinases-3 (MMP-3), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), in lipopolysaccharide (LPS)-induced MC3T3-E1 cells. Furthermore, it showed outstanding enhancement of the osteogenic activity of MC3T3-E1 cells through increased alkaline phosphatase (ALP) activity and calcium deposition. Our findings demonstrated that the BMP-2/TA/PCL scaffold plays an important role in scavenging ROS, suppressing inflammatory response, and enhancing the osteogenic differentiation of cells.


Asunto(s)
Antiinflamatorios/farmacología , Antioxidantes/farmacología , Proteína Morfogenética Ósea 2/farmacología , Osteogénesis/efectos de los fármacos , Poliésteres/química , Taninos/química , Andamios del Tejido/química , Fosfatasa Alcalina/metabolismo , Animales , Calcio/metabolismo , Línea Celular , Supervivencia Celular/efectos de los fármacos , Liberación de Fármacos , Lipopolisacáridos/farmacología , Ratones , Espectroscopía de Fotoelectrones , ARN Mensajero/genética , ARN Mensajero/metabolismo , Especies Reactivas de Oxígeno/metabolismo
10.
Int J Mol Sci ; 19(3)2018 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-29534523

RESUMEN

Tendon rupture induces an inflammatory response characterized by release of pro-inflammatory cytokines and impaired tendon performance. This study sought to investigate the therapeutic effects of simvastatin-loaded porous microspheres (SIM/PMSs) on inflamed tenocytes in vitro and collagenase-induced Achilles tendinitis in vivo. The treatment of SIM/PMSs in lipopolysaccharide (LPS)-treated tenocytes reduced the mRNA expressions of pro-inflammatory cytokines (Matrix metalloproteinase-3 (MMP-3), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)). In addition, the local injection of SIM/PMSs into the tendons of collagenase-induced Achilles tendinitis rat models suppressed pro-inflammatory cytokines (MMP-3, COX-2, IL-6, TNF-α, and MMP-13). This local treatment also upregulated anti-inflammatory cytokines (IL-4, IL-10, and IL-13). Furthermore, treatment with SIM/PMSs also improved the alignment of collagen fibrils and effectively prevented collagen disruption in a dose-dependent manner. Therefore, SIM/PMSs treatment resulted in an incremental increase in the collagen content, stiffness, and tensile strength in tendons. This study suggests that SIM/PMSs have great potential for tendon healing and restoration in Achilles tendinitis.


Asunto(s)
Antiinflamatorios/farmacología , Microesferas , Simvastatina/farmacología , Tendinopatía/tratamiento farmacológico , Tenocitos/efectos de los fármacos , Tendón Calcáneo/patología , Animales , Antiinflamatorios/administración & dosificación , Células Cultivadas , Colágeno/genética , Colágeno/metabolismo , Colagenasas/toxicidad , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Interleucinas/genética , Interleucinas/metabolismo , Lipopolisacáridos/toxicidad , Metaloproteinasas de la Matriz/genética , Metaloproteinasas de la Matriz/metabolismo , Ratas , Ratas Sprague-Dawley , Simvastatina/administración & dosificación , Tendinopatía/etiología , Tenocitos/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo
11.
Eur Heart J ; 37(37): 2833-2844, 2016 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-26787442

RESUMEN

AIMS: Inflammation plays essential role in development of plaque disruption and coronary stent-associated complications. This study aimed to examine whether intracoronary dual-modal optical coherence tomography (OCT)-near-infrared fluorescence (NIRF) structural-molecular imaging with indocyanine green (ICG) can estimate inflammation in swine coronary artery. METHODS AND RESULTS: After administration of clinically approved NIRF-enhancing ICG (2.0 mg/kg) or saline, rapid coronary imaging (20 mm/s pullback speed) using a fully integrated OCT-NIRF catheter was safely performed in 12 atheromatous Yucatan minipigs and in 7 drug-eluting stent (DES)-implanted Yorkshire pigs. Stronger NIRF activity was identified in OCT-proven high-risk plaque compared to normal or saline-injected controls (P = 0.0016), which was validated on ex vivo fluorescence reflectance imaging. In vivo plaque target-to-background ratio (pTBR) was much higher in inflamed lipid-rich plaque compared to fibrous plaque (P < 0.0001). In vivo and ex vivo peak pTBRs correlated significantly (P < 0.0022). In vitro cellular ICG uptake and histological validations corroborated the OCT-NIRF findings in vivo. Indocyanine green colocalization with macrophages and lipids of human plaques was confirmed with autopsy atheroma specimens. Two weeks after DES deployment, OCT-NIRF imaging detected strong NIRF signals along stent struts, which was significantly higher than baseline (P = 0.0156). Histologically, NIRF signals in peri-strut tissue co-localized well with macrophages. CONCLUSION: The OCT-NIRF imaging with a clinical dose of ICG was feasible to accurately assess plaque inflammation and DES-related inflammation in a beating coronary artery. This highly translatable dual-modal molecular-structural imaging strategy could be relevant for clinical intracoronary estimation of high-risk plaques and DES biology.


Asunto(s)
Stents , Animales , Enfermedad de la Arteria Coronaria , Vasos Coronarios , Stents Liberadores de Fármacos , Humanos , Verde de Indocianina , Inflamación , Imagen Molecular , Porcinos , Tomografía de Coherencia Óptica
12.
Int J Mol Sci ; 18(3)2017 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-28282891

RESUMEN

Current clinical methods for cancer diagnosis and therapy have limitations, although survival periods are increasing as medical technologies develop. In most cancer cases, patient survival is closely related to cancer stage. Late-stage cancer after metastasis is very challenging to cure because current surgical removal of cancer is not precise enough and significantly affects bystander normal tissues. Moreover, the subsequent chemotherapy and radiation therapy affect not only malignant tumors, but also healthy tissues. Nanotechnologies for cancer treatment have the clear objective of solving these issues. Nanoparticles have been developed to more accurately differentiate early-stage malignant tumors and to treat only the tumors while dramatically minimizing side effects. In this review, we focus on recent chitosan-based nanoparticles developed with the goal of accurate cancer imaging and effective treatment. Regarding imaging applications, we review optical and magnetic resonance cancer imaging in particular. Regarding cancer treatments, we review various therapeutic methods that use chitosan-based nanoparticles, including chemo-, gene, photothermal, photodynamic and magnetic therapies.


Asunto(s)
Quitosano , Nanomedicina , Nanopartículas , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Animales , Quitosano/química , Terapia Combinada , Portadores de Fármacos , Sistemas de Liberación de Medicamentos , Detección Precoz del Cáncer/métodos , Humanos , Imagen Molecular/métodos , Imagen Multimodal/métodos , Nanopartículas/química , Nanotecnología
13.
Molecules ; 22(10)2017 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-28981451

RESUMEN

Glycol chitosan (GC) and its derivatives have been extensively investigated as safe and effective drug delivery carriers because of their unique physiochemical and biological properties. The reactive functional groups such as the amine and hydroxyl groups on the GC backbone allow for easy chemical modification with various chemical compounds (e.g., hydrophobic molecules, crosslinkers, and acid-sensitive and labile molecules), and the versatility in chemical modifications enables production of a wide range of GC-based drug carriers. This review summarizes the versatile chemical modification methods that can be used to design GC-based drug carriers and describes their recent applications in disease therapy.


Asunto(s)
Quitosano/química , Portadores de Fármacos/química , Nanopartículas/química , Animales , Antineoplásicos/administración & dosificación , Reactivos de Enlaces Cruzados/química , Terapia Genética/métodos , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Estructura Molecular , Fotoquimioterapia/métodos
14.
Int J Mol Sci ; 16(5): 10324-36, 2015 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-25955650

RESUMEN

The authors describe a new type of titanium (Ti) implant as a Modi-anodized (ANO) Ti implant, the surface of which was treated by sandblasting, acid etching (SLA), and anodized techniques. The aim of the present study was to evaluate the adhesion of MG-63 cells to Modi-ANO surface treated Ti in vitro and to investigate its osseointegration characteristics in vivo. Four different types of Ti implants were examined, that is, machined Ti (control), SLA, anodized, and Modi-ANO Ti. In the cell adhesion study, Modi-ANO Ti showed higher initial MG-63 cell adhesion and induced greater filopodia growth than other groups. In vivo study in a beagle model revealed the bone-to-implant contact (BIC) of Modi-ANO Ti (74.20%±10.89%) was much greater than those of machined (33.58%±8.63%), SLA (58.47%±12.89), or ANO Ti (59.62%±18.30%). In conclusion, this study demonstrates that Modi-ANO Ti implants produced by sandblasting, acid etching, and anodizing improve cell adhesion and bone ongrowth as compared with machined, SLA, or ANO Ti implants. These findings suggest that the application of Modi-ANO surface treatment could improve the osseointegration of dental implant.


Asunto(s)
Implantación Dental Endoósea/métodos , Implantes Dentales/efectos adversos , Oseointegración , Osteoblastos/fisiología , Animales , Adhesión Celular , Línea Celular , Implantación Dental Endoósea/efectos adversos , Implantación Dental Endoósea/instrumentación , Perros , Humanos , Osteoblastos/efectos de los fármacos , Propiedades de Superficie , Titanio/efectos adversos , Titanio/química , Titanio/farmacología
15.
Nat Mater ; 12(4): 359-66, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23416726

RESUMEN

Three-photon excitation is a process that occurs when three photons are simultaneously absorbed within a luminophore for photo-excitation through virtual states. Although the imaging application of this process was proposed decades ago, three-photon biomedical imaging has not been realized yet owing to its intrinsic low quantum efficiency. We herein report on high-resolution in vitro and in vivo imaging by combining three-photon excitation of ZnS nanocrystals and visible emission from Mn(2+) dopants. The large three-photon cross-section of the nanocrystals enabled targeted cellular imaging under high spatial resolution, approaching the theoretical limit of three-photon excitation. Owing to the enhanced Stokes shift achieved through nanocrystal doping, the three-photon process was successfully applied to high-resolution in vivo tumour-targeted imaging. Furthermore, the biocompatibility of ZnS nanocrystals offers great potential for clinical applications of three-photon imaging.


Asunto(s)
Nanopartículas/química , Sulfuros/química , Compuestos de Zinc/química , Humanos , Manganeso/química , Fantasmas de Imagen , Fotones , Células Tumorales Cultivadas
16.
Mol Pharm ; 11(5): 1450-8, 2014 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-24673659

RESUMEN

Active matrix metalloproteinase-3 (MMP-3) is a prognostic marker of rheumatoid arthritis (RA). We recently developed an MMP-3 probe that can specifically detect the active form of MMP-3. The aim of this study was to investigate whether detection and monitoring of active MMP-3 could be useful to predict therapeutic drug responses in a collagen-induced arthritis (CIA) model. During the period of treatment with drugs such as methotrexate (MTX) or infliximab (IFX), MMP-3 mRNA and protein levels were correlated with fluorescence signals in arthritic joint tissues and in the serum of CIA mice. Also, bone volume density and erosion in the knee joints and the paws of CIA mice were measured with microcomputed tomography (micro-CT), X-ray, and histology to confirm drug responses. In joint tissues and serum of CIA mice, strong fluorescence signals induced by the action of active MMP-3 were significantly decreased when drugs were applied. The decrease in RA scores in drug-treated CIA mice led to fluorescence reductions, mainly as a result of down-regulation of MMP-3 mRNA or protein. The micro-CT, X-ray, and histology results clearly showed marked decreases in bone and cartilage destruction, which were consistent with the reduction of fluorescence by down-regulation of active MMP-3 in drug-treated CIA mice. We suggest that the MMP-3 diagnostic kit could be used to detect and monitor the active form of MMP-3 in CIA mice serum during a treatment course and thereby used to predict the drug response or resistance to RA therapies at an earlier stage. We hope that monitoring of active MMP-3 levels in arthritis patients using the MMP-3 diagnostic kit will be a promising tool for drug discovery, drug development, and monitoring of drug responses in RA therapy.


Asunto(s)
Antirreumáticos/uso terapéutico , Colágeno/toxicidad , Metaloproteinasa 3 de la Matriz/metabolismo , Sondas Moleculares/metabolismo , Animales , Anticuerpos Monoclonales/uso terapéutico , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/enzimología , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/enzimología , Modelos Animales de Enfermedad , Infliximab , Metotrexato/uso terapéutico , Ratones
17.
Mar Drugs ; 12(12): 6038-57, 2014 Dec 17.
Artículo en Inglés | MEDLINE | ID: mdl-25522316

RESUMEN

Theranostics is an integrated nanosystem that combines therapeutics with diagnostics in attempt to develop new personalized treatments with enhanced therapeutic efficacy and safety. As a promising therapeutic paradigm with cutting-edge technologies, theranostic agents are able to simultaneously deliver therapeutic drugs and diagnostic imaging agents and also monitor the response to therapy. Polymeric nanosystems have been intensively explored for biomedical applications to diagnose and treat various cancers. In recent years, glycol chitosan-based nanoagents have been developed as dual-purpose materials for simultaneous diagnosis and therapy. They have shown great potential in cancer therapies, such as chemotherapeutics and nucleic acid and photodynamic therapies. In this review, we summarize the recent progress and potential applications of glycol chitosan-based fluorescent theranostic nanoagents for cancer treatments and discuss their possible underlying mechanisms.


Asunto(s)
Quitosano/farmacología , Quitosano/uso terapéutico , Colorantes Fluorescentes/farmacología , Colorantes Fluorescentes/uso terapéutico , Nanopartículas/uso terapéutico , Neoplasias/tratamiento farmacológico , Animales , Diagnóstico por Imagen/métodos , Humanos
18.
Int J Pharm ; 654: 123951, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38423154

RESUMEN

Previous studies have demonstrated the effects of theranostic agents on atherosclerotic plaques. However, there is limited information on targeted theranostics for photodynamic treatment of atherosclerosis. This study aimed to develop a macrophage-mannose-receptor-targeted photoactivatable nanoagent that regulates atherosclerosis and to evaluate its efficacy as well as safety in atherosclerotic mice. We synthesised and characterised D-mannosamine (MAN)-polyethylene glycol (PEG)-chlorin e6 (Ce6) for phototheranostic treatment of atherosclerosis. The diagnostic and therapeutic effects of MAN-PEG-Ce6 were investigated using the atherosclerotic mouse model. The hydrophobic Ce6 photosensitiser was surrounded by the hydrophilic MAN-PEG outer shell of the self-assembled nanostructure under aqueous conditions. The MAN-PEG-Ce6 was specifically internalised in macrophage-derived foam cells through receptor-mediated endocytosis. After laser irradiation, the MAN-PEG-Ce6 markedly increased singlet oxygen generation. Intravital imaging and immunohistochemistry analyses verified MAN-PEG-Ce6's specificity to plaque macrophages and its notable anti-inflammatory impact by effectively reducing mannose-receptor-positive macrophages. The toxicity assay showed that MAN-PEG-Ce6 had negligible effects on the biochemical profile and structural damage in the skin and organs. Targeted photoactivation with MAN-PEG-Ce6 thus has the potential to rapidly reduce macrophage-derived inflammatory responses in atheroma and present favourable toxicity profiles, making it a promising approach for both imaging and treatment of atherosclerosis.


Asunto(s)
Aterosclerosis , Nanopartículas , Fotoquimioterapia , Porfirinas , Humanos , Animales , Ratones , Fotoquimioterapia/métodos , Manosa , Nanopartículas/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Polietilenglicoles/química , Macrófagos , Aterosclerosis/diagnóstico por imagen , Aterosclerosis/tratamiento farmacológico , Porfirinas/química , Línea Celular Tumoral
19.
Bioconjug Chem ; 24(6): 1068-74, 2013 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-23706153

RESUMEN

The activity of rheumatoid arthritis (RA) correlates with the expression of proteases. Among several proteases, matrix metalloproteinase-3 (MMP-3) is one of the biological markers used to diagnose RA. The active form of MMP-3 is a key enzyme involved in RA-associated destruction of cartilage and bone. Thus, detection of active MMP-3 in serum or in vivo is very important for early diagnosis of RA. In this study, a soluble MMP-3 probe was prepared to monitor RA progression by detecting expression of active MMP-3 in collagen-induced arthritis (CIA) mice in vivo in both serum and fibroblast-like synoviocytes (FLSs). The MMP-3 probe exhibited strong sensitivity to MMP-3 and moderate sensitivity to MMP-7 at nanomolecular concentrations, but was not sensitive to other MMPs such as MMP-2, MMP-9, and MMP-13. In an optical imaging study, the MMP-3 probe produced early and strong NIR fluorescence signals prior to observation of erythema and swelling in CIA mice. The MMP-3 probe was able to rapidly and selectively detect and monitor active MMP-3 in diluted serum from CIA mice. Furthermore, histological data demonstrated that activated FLSs in arthritic knee joints expressed active MMP-3. Together, our results demonstrated that the MMP-3 probe may be useful for detecting active MMP-3 for diagnosis of RA. More importantly, the MMP-3 probe was able to detect active MMP-3 in diluted serum with high sensitivity. Therefore, the MMP-3 probe developed in this study may be a very promising probe, useful as a biomarker for early detection and diagnosis of RA.


Asunto(s)
Artritis Experimental/enzimología , Artritis Reumatoide/enzimología , Metaloproteinasa 3 de la Matriz/metabolismo , Membrana Sinovial/enzimología , Animales , Artritis Experimental/sangre , Artritis Experimental/metabolismo , Artritis Reumatoide/sangre , Artritis Reumatoide/metabolismo , Western Blotting , Modelos Animales de Enfermedad , Activación Enzimática , Masculino , Metaloproteinasa 3 de la Matriz/sangre , Ratones , Ratones Endogámicos DBA , Imagen Molecular , Membrana Sinovial/citología , Membrana Sinovial/metabolismo
20.
Macromol Rapid Commun ; 34(5): 399-405, 2013 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-23303665

RESUMEN

This paper describes a facile method for the preparation of porous gelatin beads with uniform pore sizes using a simple fluidic device and their application as supporting materials for cell culture. An aqueous gelatin droplet containing many uniform toluene droplets, produced in the fluidic device, is dropped into liquid nitrogen for instant freezing and the small toluene droplets evolve into pores in the gelatin beads after removal of toluene and then freeze-drying. The porous gelatin beads exhibit a uniform pore size and monodisperse diameter as well as large open pores at the surface. Fluorescence microscopy images of fibroblast-loaded gelatin beads confirm the attachment and proliferation of the cells throughout the porous gelatin beads.


Asunto(s)
Materiales Biocompatibles/química , Técnicas de Cultivo de Célula/métodos , Porosidad
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