RESUMEN
Metal-organic frameworks (MOFs) are porous materials resulting from the coordination of metal clusters or ions with organic ligands, merging macromolecular and coordination chemistry features. Among these, zeolitic imidazolate framework-8 (ZIF-8) stands out as a widely utilized MOF known for its robust stability in aqueous environments owing to the robust interaction between its constituent zinc ions (Zn2+) and 2-methylimidazole (2-MIM). ZIF-8 readily decomposes under acidic conditions, serving as a promising candidate for pH-responsive drug delivery systems. Moreover, biomimetic materials typically possess good biocompatibility, reducing immune reactions. By mimicking natural structures or surface features within the body, they enhance the targeting of nanoparticles, prolong their circulation time, and increase their bioavailability in vivo. This review explores the latest advancements in biomimetic ZIF-8 nanoparticles for drug delivery, elucidating the primary obstacles and future prospects in utilizing ZIF-8 for drug delivery applications.
Asunto(s)
Materiales Biomiméticos , Sistemas de Liberación de Medicamentos , Imidazoles , Estructuras Metalorgánicas , Nanopartículas , Zeolitas , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacocinética , Humanos , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacocinética , Zeolitas/química , Zeolitas/farmacocinética , Nanopartículas/química , Sistemas de Liberación de Medicamentos/métodos , Imidazoles/química , Imidazoles/farmacocinética , Imidazoles/administración & dosificación , Animales , Zinc/química , Zinc/farmacocinética , Zinc/administración & dosificación , Biomimética/métodos , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Concentración de Iones de HidrógenoRESUMEN
Background: Dihydroartemisinin (DHA) has emerged as a promising candidate for anticancer therapy. However, the application of DHA in clinics has been hampered by several limitations including poor bioavailability, short circulation life, and low solubility, significantly restricting its therapeutic efficacy and leading to notable side effects during the treatment. Purpose: We present DHA-loaded zeolitic imidazolate framework-8 (D-ZIF) with controllable and targeted DHA release properties, leading to enhanced antitumor effects while reducing potential side effects. Methods: D-ZIF was prepared by one-pot synthesis method using methylimidazole (MIM), Zn(NO3)2â¢6H2O and DHA. We characterized the physical and chemical properties of D-ZIF by TEM, DLS, XRD, FT-IR, and TG. We measured the drug loading efficiency and the cumulative release of DHA in different pH conditions. We evaluated the cytotoxicity of D-ZIF on renal cell carcinoma (RCC786-O), glioma cells (U251), TAX-resistant human lung adenocarcinoma (A549-TAX) cells by CCK8 in vitro. We explored the possible antitumor mechanism of D-ZIF by Western blot. We evaluated the biocompatibility and hemolysis of D-ZIF and explored the in vivo antitumor efficiency in mice model by TUNEL testing and blood biomarker evaluations. Results: D-ZIF showed rhombic dodecahedral morphology with size of 129±7.2 nm and possessed a noticeable DHA encapsulation efficiency (72.9%). After 48 hours, D-ZIF released a cumulative 70.0% of the loaded DHA at pH 6.5, and only 42.1% at pH 7.4. The pH-triggered programmed release behavior of D-ZIF could enhance anticancer effect of DHA while minimizing side effects under normal physiological conditions. Compared with the free DHA group with 31.75% of A549-TAX cell apoptosis, the percentage of apoptotic cells was approximately 76.67% in the D-ZIF group. D-ZIF inhibited tumor growth by inducing tumor cell apoptosis through the mechanism of ROS production and regulation of Nrf2/HO-1 and P38 MAPK signaling pathways. D-ZIF showed potent effects in treating tumors with high safety in vivo. Conclusion: This pH-responsive release mechanism enhanced the targeting efficiency of DHA towards tumor cells, thereby increasing drug concentration in tumor sites with negligible side effects. Herein, D-ZIF holds great promise for curing cancers with minimal adverse effects.
Asunto(s)
Antineoplásicos , Artemisininas , Resistencia a Antineoplásicos , Imidazoles , Neoplasias Pulmonares , Estructuras Metalorgánicas , Especies Reactivas de Oxígeno , Artemisininas/química , Artemisininas/farmacología , Artemisininas/farmacocinética , Animales , Humanos , Especies Reactivas de Oxígeno/metabolismo , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacocinética , Estructuras Metalorgánicas/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Ratones , Resistencia a Antineoplásicos/efectos de los fármacos , Línea Celular Tumoral , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/farmacocinética , Concentración de Iones de Hidrógeno , Células A549 , Liberación de Fármacos , Ratones Desnudos , Apoptosis/efectos de los fármacos , Ratones Endogámicos BALB C , Ensayos Antitumor por Modelo de Xenoinjerto , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Hemólisis/efectos de los fármacosRESUMEN
BACKGROUND: Insufficient radiofrequency ablation (IRFA) can promote the local recurrence and distal metastasis of residual hepatocellular carcinoma (HCC), which makes clinical treatment extremely challenging. In this study, the malignant transition of residual tumors after IRFA was explored. Then, arsenic-loaded zeolitic imidazolate framework-8 nanoparticles (As@ZIF-8 NPs) were constructed, and their therapeutic effect on residual tumors was studied. RESULTS: Our data showed that IRFA can dramatically promote the proliferation, induce the metastasis, activate the epithelial-mesenchymal transition (EMT) and accelerate the angiogenesis of residual tumors. Interestingly, we found, for the first time, that extensive angiogenesis after IRFA can augment the enhanced permeability and retention (EPR) effect and enhance the enrichment of ZIF-8 nanocarriers in residual tumors. Encouraged by this unique finding, we successfully prepared As@ZIF-8 NPs with good biocompatibility and confirmed that they were more effective than free arsenic trioxide (ATO) in sublethal heat-induced cell proliferation suppression, apoptosis induction, cell migration and invasion inhibition, and EMT reversal in vitro. Furthermore, compared with free ATO, As@ZIF-8 NPs exhibited remarkably increased therapeutic effects by repressing residual tumor growth and metastasis in vivo. CONCLUSIONS: This work provides a new paradigm for the treatment of residual HCC after IRFA.
Asunto(s)
Antineoplásicos , Arsénico , Carcinoma Hepatocelular , Imidazoles , Estructuras Metalorgánicas , Nanopartículas , Animales , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacología , Arsénico/química , Arsénico/farmacocinética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , Imidazoles/química , Imidazoles/farmacocinética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacocinética , Ratones , Nanopartículas/química , Nanopartículas/metabolismo , Ablación por Radiofrecuencia , Distribución TisularRESUMEN
Long-term use of a single fungicide increases the resistance risk and causes adverse effects on natural ecosystems. Controlled release formulations of dual fungicides with different modes of action can afford a new dimension for addressing the current issues. Based on adjustable aperture and superhigh surface area, metal-organic frameworks (MOFs) are ideal candidates as pesticide release carriers. This study used Al3+ as the metal node and 2-aminoterephthalic acid as the organic chain to prepare aluminum-based metal-organic framework material (NH2-Al-MIL-101) with "cauliflower-like" structure and high surface area of 2359.0 m2/g. Fungicides of azoxystrobin (AZOX) and diniconazole (Dini) were simultaneously encapsulated into NH2-Al-MIL-101 with the loading content of 6.71% and 29.72%, respectively. Dual fungicide delivery system of AZOX@Dini@NH2-Al-MIL-101 demonstrated sustained and pH responsive release profiles. When the maximum cumulative release rate of AZOX and Dini both reached about 90%, the release time was 46 and 136 h, respectively. Furthermore, EC50 values as well as the percentage of inhibition revealed that AZOX@Dini@NH2-Al-MIL-101 had enhanced germicidal efficacy against rice sheath blight (Rhizoctonia solani), evidenced by the synergistic ratio of 1.83. The present study demonstrates a potential application prospect in sustainable plant protection through co-delivery fungicides with MOFs as a platform.
Asunto(s)
Fungicidas Industriales , Estructuras Metalorgánicas , Pirimidinas , Rhizoctonia/crecimiento & desarrollo , Estrobilurinas , Triazoles , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacocinética , Preparaciones de Acción Retardada/farmacología , Fungicidas Industriales/química , Fungicidas Industriales/farmacocinética , Fungicidas Industriales/farmacología , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacocinética , Estructuras Metalorgánicas/farmacología , Oryza/microbiología , Enfermedades de las Plantas/microbiología , Pirimidinas/química , Pirimidinas/farmacocinética , Pirimidinas/farmacología , Estrobilurinas/química , Estrobilurinas/farmacocinética , Estrobilurinas/farmacología , Triazoles/química , Triazoles/farmacocinética , Triazoles/farmacologíaRESUMEN
Polymer nanocapsules, with a hollow structure, are increasingly finding widespread use as drug delivery carriers; however, quantitatively evaluating the bio-nano interactions of nanocapsules remains challenging. Herein, poly(ethylene glycol) (PEG)-based metal-phenolic network (MPN) nanocapsules of three sizes (50, 100, and 150 nm) are engineered via supramolecular template-assisted assembly and the effect of the nanocapsule size on bio-nano interactions is investigated using in vitro cell experiments, ex vivo whole blood assays, and in vivo rat models. To track the nanocapsules by mass cytometry, a preformed gold nanoparticle (14 nm) is encapsulated into each PEG-MPN nanocapsule. The results reveal that decreasing the size of the PEG-MPN nanocapsules from 150 to 50 nm leads to reduced association (up to 70%) with phagocytic blood cells in human blood and prolongs in vivo systemic exposure in rat models. The findings provide insights into MPN-based nanocapsules and represent a platform for studying bio-nano interactions.
Asunto(s)
Sangre/metabolismo , Estructuras Metalorgánicas/química , Nanocápsulas/química , Polietilenglicoles/química , Pirogalol/análogos & derivados , Animales , Citometría de Flujo/métodos , Oro/química , Oro/metabolismo , Oro/farmacocinética , Oro/toxicidad , Humanos , Masculino , Nanopartículas del Metal/química , Nanopartículas del Metal/toxicidad , Estructuras Metalorgánicas/metabolismo , Estructuras Metalorgánicas/farmacocinética , Estructuras Metalorgánicas/toxicidad , Ratones , Nanocápsulas/toxicidad , Tamaño de la Partícula , Polietilenglicoles/metabolismo , Polietilenglicoles/farmacocinética , Polietilenglicoles/toxicidad , Pirogalol/metabolismo , Pirogalol/farmacocinética , Pirogalol/toxicidad , Células RAW 264.7 , Ratas Sprague-DawleyRESUMEN
Metal organic frameworks (MOFs) are a unique class of smart hybrid materials that have recently attracted significant interest for catalysis, separation and biomedical applications. Different strategies have been developed to overcome the limitations of MOFs for bio-applications in order to produce a system with high biocompatibility and biodegradability. In this review, we outline the chemical and physical factors that dictate the biocompatibility and biodegradability characteristics of MOFs including the nature of the metal ions and organic ligands, size, surface properties and colloidal stability. This review includes the in vitro biodegradation and in vivo biodistribution studies of MOFs to better understand their pharmacokinetics, organ toxicity and immune response. Such studies can guide the design of future bio-friendly systems that bring us closer to safely translating these platforms into the pharmaceutical consumer market.
Asunto(s)
Materiales Biocompatibles/metabolismo , Investigación Biomédica , Estructuras Metalorgánicas/metabolismo , Animales , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacocinética , Humanos , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacocinéticaRESUMEN
The confinement effect of biological ion channels regulates the transport of molecules and ions due to angstrom-sized pores. The structure of the potassium channel has a selection region (3-4 Å), a cavity (10 Å), and a gated region, while ZIF-8 has intrinsic pores with a 3.4 Å aperture and an 11.6 Å cavity similar to those of the potassium channel. Inspired by this, we constructed the glass/ZIF-8 hybrid membrane through an electrochemical growth process to explore the kinetics of the ion transmembrane by I-V curves and electrochemical impedance spectroscopy. These complementary approaches yield highly correlated results that show that ion transportation of the ZIF-8 membrane follows Arrhenius behavior. The rates of ions are controlled by the transmembrane activation energy, in which the ionic charge and radius play an important role.
Asunto(s)
Imidazoles/farmacocinética , Estructuras Metalorgánicas/farmacocinética , Metales Alcalinotérreos/farmacocinética , Nanotecnología/métodos , Canales de Potasio/farmacocinética , Imidazoles/química , Canales Iónicos/química , Canales Iónicos/farmacocinética , Transporte Iónico/fisiología , Cinética , Estructuras Metalorgánicas/química , Metales Alcalinotérreos/química , Canales de Potasio/químicaRESUMEN
In recent years, metal-phenolic networks (MPNs) have attracted increasing attention for the engineering of multi-functional platforms because of their easy fabrication processes, excellent physicochemical properties, outstanding biocompatibility, and promising theranostic applications. In this review, we summarize recent progress in the design, synthesis, shape-control, biocompatibility evaluation, and potential theranostic applications of MPNs, especially for cancer theranostics. First, we provide an overview of various MPN systems, relevant self-assembly procedures, and shape-controllable preparation. The in vitro and in vivo biocompatibility evaluation of MPNs is also discussed, including co-incubation viability, adhesion, bio-distribution, and inflammation. Finally, we highlight the significant achievements of various MPNs for cancer theranostics, such as tumor imaging, drug delivery, photothermal therapy, radiotherapy, and chemo- and photo-dynamic therapy. This review provides a comprehensive background on the design and controllable synthesis, in vitro and in vivo biocompatibility evaluation, applications of MPNs as cancer theranostic agents, and presents an overview of the most up-to-date achievements in this field.
Asunto(s)
Estructuras Metalorgánicas/uso terapéutico , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Medicina de Precisión/métodos , Animales , Materiales Biocompatibles , Sistemas de Liberación de Medicamentos , Diseño de Fármacos , Humanos , Inflamación , Ligandos , Estructuras Metalorgánicas/síntesis química , Estructuras Metalorgánicas/farmacocinética , Ratones , Estructura Molecular , Fotoquimioterapia , Fármacos Fotosensibilizantes , Tomografía de Emisión de Positrones , Radioterapia/métodos , Relación Estructura-Actividad , Distribución TisularRESUMEN
An MIL-101(Cr) powder material was successfully prepared using the hydrothermal synthesis method, and then the original MIL-101(Cr) was combined with different mass fractions of CaCl2 using the immersion method to obtain a MIL-101(Cr)/CaCl2 composite material. The physical properties of the adsorbent were determined by X-ray powder diffraction (XRD), an N2 adsorption desorption isotherm test, and thermogravimetric analysis (TG). The water vapor adsorption performance of the metal-organic frameworks MOFs was tested with a gravimetric water vapor adsorption instrument to analyze its water vapor adsorption mechanism. Based on the SIMULINK platform in the MATLAB software, a simulation model of the coefficient of performance (COP) and cooling capacity of the adsorption refrigeration system was established, and the variation trends of the COP and cooling capacity of the adsorption refrigeration system under different evaporation/condensation/adsorption/desorption temperatures was theoretically studied. MIL101-(Cr)/CaCl2-20% was selected as the adsorption material in the adsorption refrigeration system through the physical characterization of composite materials with different CaCl2 concentrations by means of adsorption water vapor test experiments. A closed adsorption system performance test device was built based on the liquid level method. The cooling power per unit and adsorbent mass (COP and SCP) of the system were tested at different evaporation temperatures (288 K/293 K/298 K); the adsorption temperature was 298 K, the condensation temperature was 308 K, and the desorption temperature was 353 K. The experimental results showed that COP and SCP increased with the increase in the evaporation temperature. When the evaporation temperature was 298 K, the level of COP was 0.172, and the level of SCP was 136.9 W/kg. The COP and SCP of the system were tested at different adsorption temperatures (293 K/298 K/303 K); the evaporation temperature was 288 K, the condensation temperature was 308 K, and the desorption temperature was 353 K. The experimental results showed that the levels of COP and SCP decreased with the increase in the adsorption temperature. When the adsorption temperature was 293 K, the level of COP was 0.18, and the level of SCP was 142.4 W/kg.
Asunto(s)
Cloruro de Calcio/química , Cloruro de Calcio/farmacocinética , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacocinética , Adsorción , Cinética , Nitrógeno/química , Refrigeración , Vapor , Temperatura , Termogravimetría , Difracción de Rayos XRESUMEN
Selectively attenuating the protection offered by heat shock protein 90 (HSP90), which is indispensable for the stabilization of the essential regulators of cell survival and works as a cell guardian under oxidative stress conditions, is a potential approach to improve the efficiency of cancer therapy. Here, we designed a biodegradable nanoplatform (APCN/BP-FA) based on a Zr(iv)-based porphyrinic porous coordination network (PCN) and black phosphorus (BP) sheets for efficient photodynamic therapy (PDT) by enhancing the accumulation of the nanoplatforms in the tumor area and attenuating the protection of cancer cells. Owing to the favorable degradability of BP, the nanosystem exhibited accelerated the release of the HSP90 inhibitor tanespimycin (17-AAG) and an apparent promotion in the reactive oxygen species (ROS) yield of PCN as well as expedited the degradation of the PCN-laden BP nanoplatforms. Both in vitro and in vivo results revealed that the elevated amounts of ROS and reduced cytoprotection in tumor cells were caused by the nanoplatforms. This strategy may provide a promising method for attenuating cytoprotection to aid efficient photodynamic therapy.
Asunto(s)
Estructuras Metalorgánicas/química , Neoplasias/tratamiento farmacológico , Fósforo/química , Fotoquimioterapia/métodos , Animales , Benzoquinonas/química , Benzoquinonas/uso terapéutico , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos , Ácido Fólico/química , Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Proteínas HSP90 de Choque Térmico/metabolismo , Humanos , Lactamas Macrocíclicas/química , Lactamas Macrocíclicas/uso terapéutico , Estructuras Metalorgánicas/farmacocinética , Estructuras Metalorgánicas/uso terapéutico , Ratones , Nanoestructuras/química , Nanoestructuras/uso terapéutico , Neoplasias/metabolismo , Fósforo/farmacocinética , Fósforo/uso terapéutico , Porosidad , Porfirinas/química , Porfirinas/farmacocinética , Porfirinas/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto , Circonio/química , Circonio/farmacocinética , Circonio/uso terapéuticoRESUMEN
Chronic wounds are one of the most serious complications of diabetes mellitus. Even though utilizing nitric oxide (NO) as a gas medicine to repair diabetic wounds presents a promising strategy, controlling the NO release behavior in the affected area, which is vital for NO-based therapy, still remains a significant challenge. In this work, a copper-based metal-organic framework, namely, HKUST-1, has been introduced as a NO-loading vehicle, and a NO sustained release system with the core-shell structure has been designed through the electrospinning method. The results show that the NO is quantificationally and stably loaded in the HKUST-1 particles, and the NO-loaded HKUST-1 particles are well incorporated into the core layer of the coaxial nanofiber. Therefore, NO can be controllably released with an average release rate of 1.74 nmol L-1 h-1 for more than 14 days. Moreover, the additional copper ions released from the degradable HKUST-1 play a synergistic role with NO to promote endothelial cell growth and significantly improve the angiogenesis, collagen deposition as well as anti-inflammatory property in the wound bed, which eventually accelerate the diabetic wound healing. These results suggest that such a copper-based metal-organic framework material as a controllable NO-releasing vehicle is a highly efficient therapy for diabetic wounds.
Asunto(s)
Portadores de Fármacos , Estructuras Metalorgánicas , Óxido Nítrico , Cicatrización de Heridas/efectos de los fármacos , Animales , Células Cultivadas , Complicaciones de la Diabetes , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Células Endoteliales de la Vena Umbilical Humana , Humanos , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacocinética , Ratones , Ratones Endogámicos C57BL , Nanofibras/química , Nanofibras/ultraestructura , Óxido Nítrico/química , Óxido Nítrico/farmacocinética , Óxido Nítrico/farmacologíaRESUMEN
Despite the great interest in RNA therapeutics, the development of a successful gene delivery process is still a major challenge. We propose an efficient nucleic acid entrapment into the mesopores of biocompatible nanoscaled metal-organic frameworks. Their rapid cellular uptake together with RNA protection and release led to a relevant in vitro gene activity.
Asunto(s)
Portadores de Fármacos , Técnicas de Transferencia de Gen , Hierro , Estructuras Metalorgánicas , ARN , Línea Celular Tumoral , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacología , Humanos , Hierro/química , Hierro/farmacocinética , Hierro/farmacología , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacocinética , Estructuras Metalorgánicas/farmacología , ARN/química , ARN/farmacocinética , ARN/farmacologíaRESUMEN
A potential bone substitute and drug carrier system is prepared to be used in treatment of serious bone infections like osteomyelitis. Vancomycin (VAN), as an antibiotic was loaded into ZIF8 nanocrystals for a pH responsive controlled release (ZIF8/VAN). Chitosan scaffolds loaded with ZIF8/VAN were prepared by wet-spinning to obtain 3D biocompatible scaffolds. Characterization of scaffolds were performed to determine the morphology, swelling behavior and pH controlled VAN release. Antibacterial activity studies were done to investigate the effectiveness of the carrier system against Staphylococcus aureus. VAN molecule encapsulation efficiency for nanosized ZIF8 crystals was calculated as 99.3%. The results showed that the VAN loaded to ZIF8 nanocrystals was released in a pH controlled manner from the chitosan scaffolds. About 70% of the VAN was released during 8â¯h at pHâ¯5.4, while this value was 55% at pHâ¯7.4. VAN release was increased with higher dissolution of ZIF8 in acidic conditions and reached a plateau value of ~77% at the end of 48â¯h at pHâ¯5.4 conditions. ZIF8 and ZIF8/VAN chitosan scaffolds showed a strong effect in the reduction of S. aureus activity in comparison to chitosan scaffolds alone. This effect was best pronounced under pHâ¯5.4 conditions which can mimic the environment of an inflamed tissue. MC3T3-E1 preosteoblasts showed high proliferation and osteogenic activities on ZIF8 loaded chitosan scaffolds.
Asunto(s)
Antibacterianos , Medicamentos Herbarios Chinos , Estructuras Metalorgánicas , Nanopartículas , Staphylococcus aureus/crecimiento & desarrollo , Vancomicina , Animales , Antibacterianos/química , Antibacterianos/farmacocinética , Antibacterianos/farmacología , Línea Celular , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacocinética , Preparaciones de Acción Retardada/farmacología , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacocinética , Medicamentos Herbarios Chinos/farmacología , Concentración de Iones de Hidrógeno , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacocinética , Estructuras Metalorgánicas/farmacología , Ratones , Nanopartículas/química , Nanopartículas/uso terapéutico , Vancomicina/química , Vancomicina/farmacocinética , Vancomicina/farmacologíaRESUMEN
Multifunctional theranostic nanoplatforms greatly improve the accuracy and effectiveness in tumor treatments. Much effort has been made in developing advanced optical imaging-based tumor theranostic nanoplatforms. However, autofluorescence and irradiation damage of the conventional fluorescence imaging technologies as well as unsatisfied curative effects of the nanoplatforms remain great challenges against their wide applications. Herein, we constructed a novel core-shell multifunctional nanoplatform, that is, chromium-doped zinc gallogermanate (ZGGO) near-infrared (NIR) persistent luminescent nanoparticles (PLNPs) as a core and zeolitic imidazolate framework-8 (ZIF-8) as a shell (namely ZGGO@ZIF-8). The ZGGO@ZIF-8 nanoplatform possessed dual functionalities of the autofluorescence-free NIR PersL imaging as well as the pH-responsive drug delivery, thus it has high potential in tumor theranostics. Notably, the loading content of doxorubicin (DOX) in ZGGO@ZIF-8 (LC = 93.2%) was quite high, and the drug release of DOX-loaded ZGGO@ZIF-8 was accelerated in an acidic microenvironment such as tumor cells. The ZGGO@ZIF-8 opens up a new material system in the combination of PLNPs with metal-organic frameworks and may offer new opportunities for the development of advanced multifunctional nanoplatforms for tumor theranostics, chemical sensing, and optical information storage.
Asunto(s)
Doxorrubicina , Estructuras Metalorgánicas , Nanopartículas , Neoplasias , Zeolitas , Cromo/química , Cromo/farmacocinética , Cromo/farmacología , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacocinética , Preparaciones de Acción Retardada/farmacología , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacología , Humanos , Concentración de Iones de Hidrógeno , Células MCF-7 , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacocinética , Estructuras Metalorgánicas/farmacología , Nanopartículas/química , Nanopartículas/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Neoplasias/patología , Zeolitas/química , Zeolitas/farmacocinética , Zeolitas/farmacología , Zinc/química , Zinc/farmacocinética , Zinc/farmacologíaRESUMEN
Metal-organic frameworks (MOFs) have been evaluated as potential nanocarriers for intraocular incorporation of brimonidine tartrate to treat chronic glaucoma. Experimental results show that UiO-67 and MIL-100 (Fe) exhibit the highest loading capacity with values up to 50-60 wt %, whereas the performance is quite limited for MOFs with narrow cavities (below 0.8 nm, for example, UiO-66 and HKUST-1). The large loading capacity in UiO-67 is accompanied by an irreversible structural amorphization in aqueous and physiological media that promotes extended release kinetics above 12 days. Compared to the traditional drawbacks associated with the sudden release of the commercial drugs (e.g., ALPHAGAN), these results anticipate UiO-67 as a potential nanocarrier for drug delivery in intraocular therapeutics. These promising results are further supported by cytotoxicity tests using retinal photoreceptor cells (661W). Toxicity of these structures (including the metal nodes and organic ligands) for retinal cells is rather low for all samples evaluated, except for HKUST-1.
Asunto(s)
Tartrato de Brimonidina , Portadores de Fármacos , Oftalmopatías/tratamiento farmacológico , Estructuras Metalorgánicas , Compuestos Organometálicos , Animales , Tartrato de Brimonidina/química , Tartrato de Brimonidina/farmacocinética , Tartrato de Brimonidina/farmacología , Línea Celular Tumoral , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacología , Ojo/metabolismo , Ojo/patología , Oftalmopatías/metabolismo , Oftalmopatías/patología , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacocinética , Estructuras Metalorgánicas/farmacología , Ratones , Compuestos Organometálicos/química , Compuestos Organometálicos/farmacocinética , Compuestos Organometálicos/farmacologíaRESUMEN
Recently, metal-organic frameworks (MOFs) or coordination polymers have shown great potential for drug delivery, yet little has been done to study how particle size affects their tumor targeting and other in vivo features. This plight is probably due to two challenges: (1) the lack of a biocompatible method to precisely control the size of drug-loaded MOFs and (2) the lack of a robust and facile radiolabeling technique to trace particles in vivo. Here, we report a one-pot, rapid, and completely aqueous approach that can precisely tune the size of drug-loaded MOF at room temperature. A chelator-free 64Cu-labeled method was developed by taking the advantage of this rapid and aqueous synthesis. Cancer cells were found to take drug-loaded MOFs in a size-dependent manner. The in vivo biodistribution of drug-loaded MOF was analyzed with positron emission tomography imaging, which, as far as we know, was used for the first time to quantitatively evaluate MOF in living animals, unveiling that 60 nm MOF showed longer blood circulation and over 50% higher tumor accumulation than 130 nm MOF. Altogether, this size-controlled method helps to find the optimal size of MOF as a drug carrier and opens new possibilities to construct multifunctional delivery systems for cancer theranostics.
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Portadores de Fármacos , Estructuras Metalorgánicas , Neoplasias Experimentales , Nanomedicina Teranóstica , Zeolitas , Animales , Línea Celular Tumoral , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacología , Femenino , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacocinética , Estructuras Metalorgánicas/farmacología , Ratones , Ratones Endogámicos BALB C , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/patología , Zeolitas/química , Zeolitas/farmacocinética , Zeolitas/farmacologíaRESUMEN
Imaging-guided therapy has considerable potential in tumor treatment. Different treatments have been integrated to realize combinational tumor therapy with improved therapeutic efficiency. Herein, the conventional metal-organic framework (MOF) MIL-100 is utilized to load curcumin with excellent encapsulation capacity. Polydopamine-modified hyaluronic acid (HA-PDA) is coated on the MIL-100 surface to construct engineering MOF nanoparticles (MCH NPs). The HA-PDA coating not only improves the dispersibility and stability of NPs but also introduces a tumor-targeting ability to this nanosystem. A two-stage augmented photothermal conversion capability is introduced to this nanosystem by encapsulating curcumin in MIL-100 pores and then coating HA-PDA on the surface, which confer the MCH NPs with strong photothermal conversional efficiency. After being intravenously injected into xenograft HeLa tumor-bearing mice, MCH NPs prefer to accumulate at the tumor site and achieve photoacoustic imaging-guided chemo-/photothermal combinational tumor therapy, generating nearly complete tumor ablation. Engineering MOFs is an efficient platform for imaging-guided combinational tumor therapy, as confirmed by in vitro and in vivo evaluations.
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Doxorrubicina , Hipertermia Inducida , Estructuras Metalorgánicas , Nanopartículas , Neoplasias Experimentales , Técnicas Fotoacústicas , Fototerapia , Células A549 , Animales , Células CHO , Cricetulus , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacología , Células HeLa , Humanos , Ácido Hialurónico/química , Ácido Hialurónico/farmacocinética , Ácido Hialurónico/farmacología , Indoles/química , Indoles/farmacocinética , Indoles/farmacología , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacocinética , Estructuras Metalorgánicas/farmacología , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Nanopartículas/química , Nanopartículas/uso terapéutico , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/patología , Polímeros/química , Polímeros/farmacocinética , Polímeros/farmacología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Selective delivery of photosensitizers to mitochondria of cancer cells can enhance the efficacy of photodynamic therapy (PDT). Though cationic Ru-based photosensitizers accumulate in mitochondria, they require excitation with less penetrating short-wavelength photons, limiting their application in PDT. We recently discovered X-ray based cancer therapy by nanoscale metal-organic frameworks (nMOFs) via enhancing radiotherapy (RT) and enabling radiodynamic therapy (RDT). Herein we report Hf-DBB-Ru as a mitochondria-targeted nMOF for RT-RDT. Constructed from Ru-based photosensitizers, the cationic framework exhibits strong mitochondria-targeting property. Upon X-ray irradiation, Hf-DBB-Ru efficiently generates hydroxyl radicals from the Hf6 SBUs and singlet oxygen from the DBB-Ru photosensitizers to lead to RT-RDT effects. Mitochondria-targeted RT-RDT depolarizes the mitochondrial membrane to initiate apoptosis of cancer cells, leading to significant regression of colorectal tumors in mouse models. Our work establishes an effective strategy to selectively target mitochondria with cationic nMOFs for enhanced cancer therapy via RT-RDT with low doses of deeply penetrating X-rays.
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Adenocarcinoma/terapia , Quimioradioterapia/métodos , Neoplasias Colorrectales/terapia , Estructuras Metalorgánicas/uso terapéutico , Animales , Ensayos de Selección de Medicamentos Antitumorales , Estructuras Metalorgánicas/síntesis química , Estructuras Metalorgánicas/farmacocinética , Ratones Endogámicos C57BL , Mitocondrias/efectos de los fármacos , Nanoestructuras/químicaRESUMEN
In this paper, the metal organic framework (MOF) concept is contributed to rearrange the bone-seeking agent composed of carrier-free lutetium-177 (Lu-177), 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraaminomethylenephosphonate (DOTMP) and cupper (II) (Cu (II)) for preparation of a potential agent for treatment of bone metastases. The product was characterized (infra-red spectroscopy, IR, and X-ray diffraction analysis) and quality-controlled (radio-thin layer chromatography, (RTLC)). The stability and in vitro hydroxyapatite binding was checked up to 1.5 month at 37 °C in human serum. Radio-MOF crystals and radio-MOF particles that were obtained by varying the synthesizing conditions (including pH and temperature) showed similar IR patterns and similar elemental analysis results. The final product was synthesized at pH = 8, stirring at room temperature (yield >99%, RTLC, particle size: 90 ± 20 nm). Biodistribution study experiments showed interesting bone-seeking (%ID/g: 8.5%) affinity of the prepared formula with no significant liver or lung uptake. Also high accumulation of radio-complex in bone tissue was estimated by the modeling of the radiation dose delivery using radiation dose assessment resource software. This novel radio-MOF with promising therapeutic results is the first study of the usage of the MOF concept to provide a high payload of Lu-177 for treatment of bone metastases. As it was expected, the most important outcome of the paper was higher bone-uptake rates rather than conventional 177Lu-DOTMP.
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Antineoplásicos , Neoplasias Óseas/metabolismo , Estructuras Metalorgánicas , Compuestos Organometálicos , Animales , Antineoplásicos/química , Antineoplásicos/farmacocinética , Durapatita/química , Durapatita/metabolismo , Nanopartículas del Metal/química , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacocinética , Compuestos Organometálicos/química , Compuestos Organometálicos/farmacocinética , Ratas , Distribución TisularRESUMEN
Bone is the most common organ affected by metastatic breast cancer. Targeting cancers within the bone remains a great challenge due to the inefficient delivery of therapeutic to bone. In this study, a polyethylene glycol (PEG) coated nanoparticles (NPs) made of a Zn2+ coordination polymer was linked with a bone seeking moiety, alendronate (ALN), to deliver cisplatin prodrug (DSP) to the bone. The particle sizes of this novel system, DSP-Zn@PEG-ALN NPs, were regulated by adjusting the volume ratio of water phase to oil phase in microemulsion. It was small enough (about 55nm) to extravasate through the clefts (80nm) of the bone's sinusoidal capillaries and localize into metastatic bones. DSP-Zn@PEG-ALN NPs showed much higher affinity for hydroxyapatite in vitro and bone in vivo than non-targeted DSP-Zn@PEG NPs and cisplatin. In addition, the in vivo biodistribution studies demonstrated that about 4-fold of platinum was delivered to the bone metastatic lesions than that in healthy bones by DSP-Zn@PEG-ALN NPs intravenously. Finally, DSP-Zn@PEG-ALN NPs not only inhibited the tumor growth efficiently but also reduced the osteocalastic bone destruction. Besides, DSP-Zn@PEG-ALN NPs showed significantly reduced toxicity of cisplatin. These results indicate that the DSP-Zn@PEG-ALN NPs have a great potential in enhancing chemotherapeutic efficacy for the treatment of bone metastatic breast cancer.