RESUMO
Nitric oxide (NO) is an endogenous gasotransmitter regulating alternative physiological processes in the cardiovascular system. To achieve translational application of NO, continued efforts are made on the development of orally active NO prodrugs for long-term treatment of chronic cardiovascular diseases. Herein, immobilization of NO-delivery [Fe2(µ-SCH2CH2COOH)2(NO)4] (DNIC-2) onto MIL-88B, a metal-organic framework (MOF) consisting of biocompatible Fe3+ and 1,4-benzenedicarboxylate (BDC), was performed to prepare a DNIC@MOF microrod for enhanced oral delivery of NO. In simulated gastric fluid, protonation of the BDC linker in DNIC@MOF initiates its transformation into a DNIC@tMOF microrod, which consisted of DNIC-2 well dispersed and confined within the BDC-based framework. Moreover, subsequent deprotonation of the BDC-based framework in DNIC@tMOF under simulated intestinal conditions promotes the release of DNIC-2 and NO. Of importance, this discovery of transformer-like DNIC@MOF provides a parallel insight into its stepwise transformation into DNIC@tMOF in the stomach followed by subsequent conversion into molecular DNIC-2 in the small intestine and release of NO in the bloodstream of mice. In comparison with acid-sensitive DNIC-2, oral administration of DNIC@MOF results in a 2.2-fold increase in the oral bioavailability of NO to 65.7% in mice and an effective reduction of systolic blood pressure (SBP) to a ΔSBP of 60.9 ± 4.7 mmHg in spontaneously hypertensive rats for 12 h.
Assuntos
Materiais Biocompatíveis/farmacologia , Estruturas Metalorgânicas/farmacologia , Óxido Nítrico/química , Pró-Fármacos/farmacologia , Administração Oral , Animais , Materiais Biocompatíveis/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Eletrodos , Concentração de Íons de Hidrogênio , Teste de Materiais , Estruturas Metalorgânicas/administração & dosagem , Camundongos , Óxido Nítrico/administração & dosagem , Tamanho da Partícula , Pró-Fármacos/química , Propriedades de SuperfícieRESUMO
Patches with the capacity of controllable delivering active molecules toward the wound bed to promote wound healing are expectant all along. Herein, a novel porous metal-organic framework (MOF) microneedle (MN) patch enabling photothermal-responsive nitric oxide (NO) delivery for promoting diabetic wound healing is presented. As the NO-loadable copper-benzene-1,3,5-tricarboxylate (HKUST-1) MOF is encapsulated with graphene oxide (GO), the resultant NO@HKUST-1@GO microparticles (NHGs) are imparted with the feature of near-infrared ray (NIR) photothermal response, which facilitate the controlled release of NO molecules. When these NHGs are embedded in a porous PEGDA-MN, the porous structure, larger specific surface area, and sufficient mechanical strength of the integrated MN could promote a more accurate and deeper delivery of NO molecules into the wound site. By applying the resultant NHG-MN to the wound of a type I diabetic rat model, the authors demonstrate that it is capable of accelerating vascularization, tissue regeneration, and collagen deposition, indicating its bright prospect applied in wound healing and other therapeutic scenarios.
Assuntos
Estruturas Metalorgânicas/química , Óxido Nítrico/administração & dosagem , Terapia Fototérmica/métodos , Cicatrização/fisiologia , Animais , Modelos Animais de Doenças , Estruturas Metalorgânicas/administração & dosagem , Agulhas , Porosidade , RatosRESUMO
BACKGROUND: The complex tumor microenvironment and non-targeting drugs limit the efficacy of clinical tumor therapy. For ensuring the accurate delivery and maximal effects of anticancer drugs, it is important to develop innovative drug delivery system based on nano-strategies. RESULT: In this study, an intracellular acidity-responsive polymeric metal organic framework nanoparticle (denoted as DIMP) has been constructed, which can co-deliver the chemotherapy agent of doxorubicin (DOX) and phototherapy agent of indocyanine green (ICG) for breast carcinoma theranostics. Specifically, DIMP possesses a suitable and stable nanometer size and can respond to the acidic microenvironment in cells, thus precisely delivering drugs into target tumor sites and igniting the biological reactions towards cell apoptosis. Following in vivo and in vitro results showed that DIMP could be effectively accumulated in tumor sites and induced powerful immunogenic cell death (ICD) effect. CONCLUSION: The designed DIMP displayed its effectiveness in combined photo-chemotherapy with auxiliary of ICD effect under a multimodal imaging monitor. Thus, the present MOF-based strategy may offer a potential paradigm for designing drug-delivery system for image-guided synergistic tumor therapy.
Assuntos
Antineoplásicos/administração & dosagem , Morte Celular Imunogênica/efeitos dos fármacos , Estruturas Metalorgânicas/administração & dosagem , Nanopartículas/administração & dosagem , Microambiente Tumoral/efeitos dos fármacos , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/terapia , Linhagem Celular Tumoral , Terapia Combinada , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Feminino , Verde de Indocianina/administração & dosagem , Verde de Indocianina/química , Verde de Indocianina/farmacologia , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Camundongos , Imagem Multimodal , Nanopartículas/química , FototerapiaRESUMO
Polyurethane foams (PUFs) have attracted attention as biomaterials because of their low adhesion to the wound area and suitability as biodegradable or bioactive materials. The composition of the building blocks for PUFs can be controlled with additives, which provide excellent anti-drug resistance and biocompatibility. Herein, nanosized Cu-BTC (copper(II)-benzene-1,3,5-tricarboxylate) was incorporated into a PUF via the crosslinking reaction of castor oil and chitosan with toluene-2,4-diisocyanate, to enhance therapeutic efficiency through the modification of the surface of PUF. The physical and thermal properties of the nanosized Cu-BTC-incorporated PUF (PUF@Cu-BTC), e.g., swelling ratio, phase transition, thermal gravity loss, and cell morphology, were compared with those of the control PUF. The bactericidal activities of PUF@Cu-BTC and control PUF were evaluated against Pseudomonas aeruginosa, Klebsiella pneumoniae, and methicillin-resistant Staphylococcus aureus. PUF@Cu-BTC exhibited selective and significant antibacterial activity toward the tested bacteria and lower cytotoxicity for mouse embryonic fibroblasts compared with the control PUF at a dose of 2 mg mL-1. The Cu(II) ions release test showed that PUF@Cu-BTC was stable in phosphate buffered saline (PBS) for 24 h. The selective bactericidal activity and low cytotoxicity of PUF@Cu-BTC ensure it is a candidate for therapeutic applications for the drug delivery, treatment of skin disease, and wound healing.
Assuntos
Antibacterianos/administração & dosagem , Materiais Biocompatíveis/química , Cobre/administração & dosagem , Estruturas Metalorgânicas/administração & dosagem , Poliuretanos/química , Antibacterianos/química , Antibacterianos/farmacologia , Cobre/química , Cobre/farmacologia , Portadores de Fármacos/química , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/prevenção & controle , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacosRESUMO
Tuberculosis (TB) is an infectious disease that causes a great number of deaths in the world (1.5 million people per year). This disease is currently treated by administering high doses of various oral anti-TB drugs for prolonged periods (up to 2 years). While this regimen is normally effective when taken as prescribed, many people with TB experience difficulties in complying with their medication schedule. Furthermore, the oral administration of standard anti-TB drugs causes severe side effects and widespread resistances. Recently, we proposed an original platform for pulmonary TB treatment consisting of mannitol microspheres (Ma MS) containing iron (III) trimesate metal-organic framework (MOF) MIL-100 nanoparticles (NPs). In the present work, we loaded this system with the first-line anti-TB drug isoniazid (INH) and evaluated both the viability and safety of the drug vehicle components, as well as the cell internalization of the formulation in alveolar A549 cells. Results show that INH-loaded MOF (INH@MIL-100) NPs were efficiently microencapsulated in Ma MS, which displayed suitable aerodynamic characteristics for pulmonary administration and non-toxicity. MIL-100 and INH@MIL-100 NPs were efficiently internalized by A549 cells, mainly localized in the cytoplasm. In conclusion, the proposed micro-nanosystem is a good candidate for the pulmonary administration of anti-TB drugs.
Assuntos
Antituberculosos/farmacologia , Isoniazida/farmacologia , Estruturas Metalorgânicas/farmacologia , Tuberculose Pulmonar/tratamento farmacológico , Células A549 , Administração por Inalação , Antituberculosos/administração & dosagem , Antituberculosos/química , Cápsulas/administração & dosagem , Cápsulas/química , Cápsulas/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Isoniazida/administração & dosagem , Isoniazida/química , Estruturas Metalorgânicas/administração & dosagem , Estruturas Metalorgânicas/química , Tamanho da PartículaRESUMO
INTRODUCTION: The development of multidrug resistance (MDR) is a major cause for the failure of chemotherapy, which requires the aid of nanomedicine. METHODS: Here in our study, a Cu2+ based metal-organic framework (COF) was firstly developed and employed as a carrier for the delivery of glucose oxidase (GOx) and doxorubicin (Dox) (COF/GOx/Dox) for the therapy of MDR lung cancers. RESULTS: Our results showed that the GOx can catalyze glucose and produce H2O2. In the mean time, the Cu2+ can react with GSH and then transform into Cu+, which resulted in GSH depletion. Afterwards, the produced Cu+ and H2O2 trigger Fenton reaction to generate ROS to damage the redox equilibrium of cancer cells. Both effects contributed to the reverse of MDR in A549/Dox cells and finally resulted in significantly enhanced in vitro/in vivo anticancer performance. DISCUSSION: The combination of glutathione depletion/reactive oxygen species elevation might be a promising strategy to enhance the efficacy of chemotherapy and reverse MDR in cancers.
Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Cobre/administração & dosagem , Glucose Oxidase/administração & dosagem , Glutationa/metabolismo , Estruturas Metalorgânicas/administração & dosagem , Espécies Reativas de Oxigênio/metabolismo , Células A549 , Animais , Cobre/química , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Doxorrubicina/síntese química , Glucose Oxidase/síntese química , Glutationa/antagonistas & inibidores , Humanos , Masculino , Estruturas Metalorgânicas/síntese química , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Oxirredução/efeitos dos fármacos , Coelhos , Ensaios Antitumorais Modelo de Xenoenxerto/métodosRESUMO
Owing to their facile synthesis, tailorable porosity, diverse compositions, and low toxicity, zeolitic imidazolate framework (ZIF) nanoparticles (NPs) have emerged as attractive platforms for a variety of biologically relevant applications. To date, a small subset of ZIFs representing only two topologies and very few linker chemistries have been studied in this realm. We seek to expand the bio-design space for ZIF NPs through the targeted synthesis of a hierarchically complex ZIF based on two types of cages, ZIF-20, with lta topology. This study demonstrates the rapid synthesis and size tunability of ZIF-20 particles across the micro and nanoregimes via microwave heating and the use of a modulating agent. To evaluate the utility of ZIF particles for biological applications, we examine their stability in biologically relevant media and demonstrate biocompatibility with A549 human epithelial cells. Further, the ability to encapsulate and release methylene blue, a therapeutic and bioimaging agent, is validated. Importantly, ZIF-20 NPs display a unique behavior relative to previously studied ZIFs based on their specific structural and chemical features. This finding highlights the need to expand the design space across the broader ZIFs family, to exploit a wider range of relevant properties for biological applications and beyond.
Assuntos
Imidazóis/química , Neoplasias Pulmonares/metabolismo , Estruturas Metalorgânicas/administração & dosagem , Azul de Metileno/metabolismo , Nanopartículas/administração & dosagem , Zeolitas/química , Células A549 , Sobrevivência Celular , Humanos , Neoplasias Pulmonares/patologia , Estruturas Metalorgânicas/química , Nanopartículas/químicaRESUMO
Nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S) are gaseous signaling molecules (gasotransmitters) that regulate both physiological and pathological processes and offer therapeutic potential for the treatment of many diseases, such as cancer, cardiovascular disease, renal disease, bacterial and viral infections. However, the inherent labile nature of therapeutic gases results in difficulties in direct gases administration and their controlled delivery at clinically relevant ranges. Metal-organic frameworks (MOFs) with highly porous, stable, and easy-to-tailor properties have shown promising therapeutic gas delivery potential. Herein, we highlight the recent advances of MOF-based platforms for therapeutic gas delivery, either by endogenous (i.e., direct transfer of gases to targets) or exogenous (i.e., stimulating triggered release of gases) means. Reports that involve in vitro and/or in vivo studies are highlighted due to their high potential for clinical translation. Current challenges for clinical requirements and possible future innovative designs to meet variable healthcare needs are discussed.
Assuntos
Gasotransmissores/administração & dosagem , Estruturas Metalorgânicas/administração & dosagem , Animais , Monóxido de Carbono/administração & dosagem , Humanos , Sulfeto de Hidrogênio/administração & dosagem , Óxido Nítrico/administração & dosagem , Oxigênio/administração & dosagemRESUMO
Chemotherapeutic agents used in treating certain cancer types operate in a non-selective manner tending to accumulate in normal, healthy tissue when high doses are used. To mitigate the toxicity effect resulting from this, there is an urgent need to develop active nano delivery systems capable of regulating optimal doses specifically to cancer cells without harming adjacent normal cells. Herein, we report a versatile nanoparticle - zeolitic imidazolate framework-8 (nZIF-8) - that is loaded with a chemotherapeutic agent (gemcitabine; GEM) and surface-functionalized with an autonomous homing system (Arg-Gly-Asp peptide ligand; RGD) via a straightforward, one-pot solvothermal reaction. Successful functionalization of the surface of nZIF-8 loaded GEM (GEMânZIF-8) with RGD was proven by spectroscopic and electron microscopy techniques. This surface-functionalized nanoparticle (GEMâRGD@nZIF-8) exhibited enhanced uptake in human lung cancer cells (A549), compared with non-functionalized GEMânZIF-8. The GEMâRGD@nZIF-8, experienced not only efficient uptake within A549, but also induced obvious cytotoxicity (75% at a concentration of 10 µg mL-1) and apoptosis (62%) after 48 h treatment when compared to the nanoparticle absent of the RGD homing system (GEMânZIF-8). Most importantly, this surface-functionalized nanoparticle was more selective towards lung cancer cells (A549) than normal human lung fibroblast cells (MRC-5) with a selectivity index (SI) of 3.98. This work demonstrates a new one-pot strategy for realizing a surface-functionalized zeolitic imidazolate framework that actively targets cancer cells via an autonomous homing peptide system to deliver a chemotherapeutic payload effectively.
Assuntos
Antineoplásicos , Desoxicitidina/análogos & derivados , Imidazóis , Neoplasias Pulmonares/tratamento farmacológico , Estruturas Metalorgânicas , Nanopartículas , Oligopeptídeos , Zeolitas , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Desoxicitidina/administração & dosagem , Desoxicitidina/química , Humanos , Imidazóis/administração & dosagem , Imidazóis/química , Estruturas Metalorgânicas/administração & dosagem , Estruturas Metalorgânicas/química , Nanopartículas/administração & dosagem , Nanopartículas/química , Oligopeptídeos/administração & dosagem , Oligopeptídeos/química , Propriedades de Superfície , Zeolitas/administração & dosagem , Zeolitas/química , GencitabinaRESUMO
The coordination polymer CPO-27-Mg was rapidly synthesized under microwave irradiation. This material exhibits a sufficiently high drug loading towards aspirin (~8% wt.) and paracetamol (~14% wt.). The binding of these two molecules with the inner surface of the metal-organic framework was studied employing the Gaussian and Plane Wave approach of the Density Functional Theory. The structure of CPO-27-Mg persists after the adsorption of aspirin or paracetamol and their desorption energies, being quite high, decrease under solvent conditions.
Assuntos
Portadores de Fármacos/síntese química , Sistemas de Liberação de Medicamentos/métodos , Estruturas Metalorgânicas/síntese química , Micro-Ondas , Acetaminofen/administração & dosagem , Acetaminofen/química , Analgésicos não Narcóticos/administração & dosagem , Analgésicos não Narcóticos/química , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Aspirina/administração & dosagem , Aspirina/química , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Estruturas Metalorgânicas/administração & dosagem , Estruturas Metalorgânicas/química , Compostos Organometálicos/administração & dosagem , Compostos Organometálicos/síntese química , Compostos Organometálicos/químicaRESUMO
Nano metal organic frameworks (NMOFs) belong to the group of nanoporous materials. Over the decades, the conducted researches explored the area for the potential applications of NMOFs in areas like biomedical, chemical engineering and materials science. Recently, NMOFs have been explored for their potential use in cancer diagnosis and therapeutics. The excellent physico-chemical features of NMOFs also make them a potential candiadate to facilitate drug design, delivery and storage against cancer cells. In this review, we have explored the characterstic features, synthesis methods, NMOFs based drug delivery, diagnosis and imaging in various cancer types. In addition to this, we have also pondered on the stability and toxicological concerns of NMOFs. Despite, a significant research has been done for the potential use of NMOFs in cancer diagonostic and therapeutics, more information regarding the stability, in-vivo clearance, toxicology, and pharmacokinetics is still needed to ehnace the use of NMOFs in cancer diagonostic and therapeutics.
Assuntos
Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos , Estruturas Metalorgânicas/administração & dosagem , Nanomedicina , Nanopartículas/administração & dosagem , Neoplasias/tratamento farmacológico , Animais , Humanos , Estruturas Metalorgânicas/química , Nanopartículas/química , Neoplasias/patologiaRESUMO
Oral administration of medicine faces physiological constraints imposed by the gastrointestinal tract (GIT) and simultaneously causes irritation to GI mucosa, which motivates us to pursue the innovation of a GI drug delivery system. Inspired by the mucosa-nutrient functions of Zinc element and smectite clay, a montmorillonite (MMT)-enveloped zeolitic imidazolate framework (M-ZIF-8) is developed in a successive one-pot fabrication of ZIF-8 encapsulated medicine, and followed MMT coating to yield a core-shell nanoplatform for GI drug delivery. ZIF-8 encapsulated medicines can maintain their intrinsic structure, and MMT layer potentiates mucous-adhesion and optimizes medicine release. Validated in gastritis and colitis models, M-ZIF-8 not only achieves efficient GI delivery of nonsteroidal anti-inflammatory drugs (NSAIDs) for inflammation inhibition, but also reduces the NSAIDs-induced GI irritation, promoting mucosal healing in GIT. Coupled with the facile construction and biocompatibility, M-ZIF-8 shows a significant advancement in GI drug delivery.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Bentonita/química , Sistemas de Liberação de Medicamentos , Fármacos Gastrointestinais/farmacologia , Trato Gastrointestinal/efeitos dos fármacos , Estruturas Metalorgânicas/química , Administração Oral , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Sulfato de Dextrana , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/química , Trato Gastrointestinal/metabolismo , Humanos , Imidazóis/administração & dosagem , Imidazóis/química , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Masculino , Estruturas Metalorgânicas/administração & dosagem , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Estrutura Molecular , Tamanho da Partícula , Propriedades de Superfície , Células Tumorais Cultivadas , Zeolitas/administração & dosagem , Zeolitas/químicaRESUMO
Although nanoscaled metal-organic frameworks (nanoMOFs) are promising drug carriers, their appropriate formulation remains almost unexplored and basically restricted to intravenous routes. Lungs, beneficiating from a large absorption surface and low enzymatic presence, are a very attractive target for both local and systemic delivery. However, pulmonary nanoMOF formulation is a pending and defying task. Thus, we propose a pioneer nanoMOF-based microsphere system as a potential platform for pulmonary administration. A biocompatible nanoMOF was successfully encapsulated in mannitol by a simple and continuous spray-drying technique. Upon intratracheal administration to rats, the resulting formulation, exhibiting optimal properties (i.e., homogeneity, size, density, and spray-drying process yield), was able to release the intact nanoMOF carrier uniformly along the lungs, reaching the bronchioles and alveoli.
Assuntos
Sistemas de Liberação de Medicamentos/métodos , Excipientes/química , Estruturas Metalorgânicas/química , Microesferas , Administração por Inalação , Animais , Dextranos/química , Manitol/química , Estruturas Metalorgânicas/administração & dosagem , Estudo de Prova de Conceito , Ratos Wistar , alfa-Ciclodextrinas/químicaRESUMO
Coordinative interactions between multivalent metal ions and drug derivatives with Lewis base functions give rise to nanoscale coordination polymers (NCPs) as delivery systems. As the pharmacologically active agent constitutes a main building block of the nanomaterial, the resulting drug loadings are typically very high. By additionally selecting metal ions with favorable pharmacological or physicochemical properties, the obtained NCPs are predominantly composed of active components which serve individual purposes, such as pharmacotherapy, photosensitization, multimodal imaging, chemodynamic therapy or radiosensitization. By this approach, the assembly of drug molecules into NCPs modulates pharmacokinetics, combines pharmacological drug action with specific characteristics of metal components and provides a strategy to generate tailorable multifunctional nanoparticles. This article reviews different applications and recent examples of such highly functional nanopharmaceuticals with a high 'material economy'. Lay Summary: Nanoparticles, that are small enough to circulate in the bloodstream and can carry cargo molecules, such as drugs, imaging or contrast agents, are attractive materials for pharmaceutical applications. A high loading capacity is a generally aspired parameter of nanopharmaceuticals to minimize patient exposure to unnecessary nanomaterial. Pharmaceutical agents containing Lewis base functions in their molecular structure can directly be assembled into metal-organic nanopharmaceuticals by coordinative interaction with metal ions. Such coordination polymers generally feature extraordinarily high loading capacities and the flexibility to encapsulate different agents for a simultaneous delivery in combination therapy or 'theranostic' applications.
Assuntos
Produtos Biológicos/administração & dosagem , Portadores de Fármacos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Estruturas Metalorgânicas/administração & dosagem , Nanopartículas/administração & dosagem , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/metabolismo , Produtos Biológicos/química , Produtos Biológicos/metabolismo , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Humanos , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/metabolismo , Nanopartículas/química , Nanopartículas/metabolismoRESUMO
Oral insulin delivery has revolutionized diabetes treatment, but challenges including degradation in the gastrointestinal environment and low permeation across the intestinal epithelium remain. Herein, to overcome these barriers, we developed a novel biodegradable nanocomposite microsphere embedded with metal-organic framework (MOF) nanoparticles. An iron-based MOF nanoparticle (NP) (MIL-100) was first synthesized as a carrier with an insulin loading capacity of 35%. The insulin-loaded MIL-100 nanoparticles modified with sodium dodecyl sulfate (Ins@MIL100/SDS) promoted insulin permeation across Caco-2 monolayer models in vitro. To improve resistance to the gastric acid environment, Ins@MIL100/SDS nanoparticles were embedded into a biodegradable microsphere to construct the nanocomposite delivery system (Ins@MIL100/SDS@MS). The microspheres effectively protected the MOF NPs from rapid degradation under acidic conditions and could release insulin-loaded MOF NPs in the simulated intestinal fluid. After the oral administration of Ins@MIL100/SDS@MS into BALB/c nude mice, increased intestinal absorption of the insulin was detected compared to the oral administration of free insulin or Ins@MIL100/SDS. Furthermore, significantly enhanced plasma insulin levels were obtained for over 6 h after oral administration of Ins@MIL100/SDS@MS into diabetic rats, leading to a remarkably enhanced effect in lowering blood glucose level with a relative pharmacological availability of 7.8%. Thus, the MOF-nanoparticle-incorporated microsphere may provide a new strategy for effective oral protein delivery.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Portadores de Fármacos/química , Hipoglicemiantes/uso terapêutico , Insulina Regular de Porco/uso terapêutico , Estruturas Metalorgânicas/química , Nanocompostos/química , Administração Oral , Animais , Plásticos Biodegradáveis/química , Células CACO-2 , Portadores de Fármacos/administração & dosagem , Liberação Controlada de Fármacos , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/química , Hipoglicemiantes/farmacocinética , Insulina Regular de Porco/administração & dosagem , Insulina Regular de Porco/química , Insulina Regular de Porco/farmacocinética , Masculino , Estruturas Metalorgânicas/administração & dosagem , Camundongos Endogâmicos BALB C , Microesferas , Nanocompostos/administração & dosagem , Nanopartículas/administração & dosagem , Nanopartículas/química , Poliésteres/administração & dosagem , Poliésteres/química , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/química , Ratos Wistar , SuínosRESUMO
We design multifunctional CDDP-VPA@ZrMOF-Cys-PEG nanoparticles (CVZP NPs) based on the properties of valproic acid (VPA) that can downregulate the expression of vascular endothelial growth factor (VEGF) to reduce the drug resistance of tumor cells. In vivo experiments confirm that chemotherapy combined with microwave thermal therapy (MWTT) can significantly improve the therapeutic effect of cisplatin-resistant lung cancer.
Assuntos
Antineoplásicos/administração & dosagem , Cisplatino/administração & dosagem , Cisteína/administração & dosagem , Sistemas de Liberação de Medicamentos , Neoplasias Pulmonares/tratamento farmacológico , Estruturas Metalorgânicas/administração & dosagem , Nanopartículas/administração & dosagem , Ácido Valproico/administração & dosagem , Zircônio/administração & dosagem , Animais , Antineoplásicos/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/química , Cisteína/química , Resistencia a Medicamentos Antineoplásicos , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Estruturas Metalorgânicas/química , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos ICR , Camundongos Nus , Nanopartículas/química , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/química , Carga Tumoral/efeitos dos fármacos , Ácido Valproico/química , Fator A de Crescimento do Endotélio Vascular/metabolismo , Zircônio/químicaRESUMO
BACKGROUND: Photoreceptor degeneration is one of the most refractory oculopathy in the world, leading to vision loss in severe cases. Methyprednisolone is one of the most commonly prescribed medications for the treatment of retinal degenerative diseases, either by oral administration or repeated intraocular injections. However, the efficacy was unsatisfactory due to its systemic or local side effects and short retention time within the retina. METHODS: Nanoscale zirconium-porphyrin metal-organic framework (NPMOF) was synthesized and characterized. The biotoxicity and imaging capability of NPMOF were evaluated using zebrafish embryos and larvae. NPMOF was then used as a skeleton and loaded with methylprednisolone (MPS) to prepare a novel kind of nanoparticle, MPS-NPMOF. Photoreceptor degeneration was induced by high-intensity light exposure in adult zebrafish. MPS-NPMOF was delivered to the injured retina by intraocular injection. The photoreceptor regeneration and its underlying mechanism were explored by immunohistochemistry, quantitative real-time polymerase chain reaction and behavioral test. RESULTS: NPMOF not only had low biotoxicity but also emitted bright fluorescence. Following a single MPS-NPMOF intraocular injection, the injured retina exhibited the faster photoreceptor regeneration with better visual function by promoting the cell proliferation. CONCLUSION: NPMOF is an ideal carrier and could be applied in tracking and delivering medications. By intraocular injection, the novel drug delivery system, MPS-NPMOF, accomplishes the sustained release of drug and plays a therapeutic role in photoreceptor degeneration.
Assuntos
Sistemas de Liberação de Medicamentos/métodos , Estruturas Metalorgânicas/química , Metilprednisolona/administração & dosagem , Porfirinas/química , Degeneração Retiniana/tratamento farmacológico , Zircônio/química , Animais , Animais Geneticamente Modificados , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Embrião não Mamífero/efeitos dos fármacos , Fluorescência , Injeções Intraoculares , Estruturas Metalorgânicas/administração & dosagem , Estruturas Metalorgânicas/farmacologia , Metilprednisolona/farmacologia , Nanoestruturas/administração & dosagem , Nanoestruturas/química , Células Fotorreceptoras de Vertebrados/metabolismo , Retina/efeitos dos fármacos , Retina/lesões , Degeneração Retiniana/etiologia , Peixe-Zebra/embriologiaRESUMO
Uniform micron sized hierarchical COF (HCOF) spheres were fabricated by a template-free solution-based aging method at room temperature for the first time. The postsynthetic metalation of HCOF with Fe3+ makes the metalated HCOF an excellent photothermal agent (PTA) for photothermal therapy (PTT).
Assuntos
Antineoplásicos/farmacologia , Estruturas Metalorgânicas/farmacologia , Fototerapia , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Estruturas Metalorgânicas/administração & dosagem , Estruturas Metalorgânicas/química , Camundongos , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Imagem Óptica , Tamanho da Partícula , Propriedades de SuperfícieRESUMO
The application of photothermal therapy to treat bacterial infections remains a challenge, as the high temperatures required for bacterial elimination can damage healthy tissues. Here, we develop an exogenous antibacterial agent consisting of zinc-doped Prussian blue (ZnPB) that kills methicillin-resistant Staphylococcus aureus in vitro and in a rat model of cutaneous wound infection. Local heat triggered by the photothermal effect accelerates the release and penetration of ions into the bacteria, resulting in alteration of intracellular metabolic pathways and bacterial killing without systemic toxicity. ZnPB treatment leads to the upregulation of genes involved in tissue remodeling, promotes collagen deposition and enhances wound repair. The efficient photothermal conversion of ZnPB allows the use of relatively few doses and low laser flux, making the platform a potential alternative to current antibiotic therapies against bacterial wound infections.
Assuntos
Antibacterianos/administração & dosagem , Terapia a Laser , Estruturas Metalorgânicas/administração & dosagem , Infecções Estafilocócicas/terapia , Infecção dos Ferimentos/terapia , Administração Cutânea , Animais , Antibacterianos/química , Terapia Combinada/métodos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Ferrocianetos/administração & dosagem , Ferrocianetos/química , Humanos , Raios Infravermelhos/uso terapêutico , Masculino , Estruturas Metalorgânicas/química , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana , Células NIH 3T3 , Nanopartículas/administração & dosagem , Nanopartículas/química , Ratos , Infecções Estafilocócicas/microbiologia , Resultado do Tratamento , Cicatrização/efeitos dos fármacos , Cicatrização/efeitos da radiação , Infecção dos Ferimentos/microbiologia , Zinco/administração & dosagem , Zinco/químicaRESUMO
Since current subunit vaccines are limited by a short half-life in vivo and weak immune responses when used alone without adjuvants, there is an unmet need for combing carriers with complement activation signals to interrupt outbreaks in real-time. Amino-functionalized zirconium-based MOFs (UiO-AM) could activate the complement system, which plays an important role in innate and adaptive immunity. Our data provide design principles for studies on complement activation as a safe vaccine carrier that can effectively enhance immune responses against antigens in vivo.