RESUMEN
Herein, we report a composite COF material loaded with a Pt nanoenzyme and an organic photosensitizer BODIPY, synthesized via a stepwise post-synthetic modification. The obtained Pt@COF-BDP nanoparticles can efficiently and continuously convert H2O2 to O2, thereby increasing the efficiency of single-linear oxygen production and achieving efficient tumor inhibition.
Asunto(s)
Compuestos de Boro , Estructuras Metalorgánicas , Fotoquimioterapia , Fármacos Fotosensibilizantes , Platino (Metal) , Compuestos de Boro/química , Compuestos de Boro/farmacología , Humanos , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/síntesis química , Platino (Metal)/química , Platino (Metal)/farmacología , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Estructuras Metalorgánicas/síntesis química , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular Tumoral , Ratones , Nanopartículas/química , Hipoxia Tumoral/efectos de los fármacos , Peróxido de Hidrógeno/químicaRESUMEN
Herein, we report an indocyanine green (ICG)-decorated and glucose oxidase (GOx)-loaded nanoscale composite COF material via a stepwise post-synthetic modification. The obtained GOx@COF-ICG can achieve synergistic inhibition of intracellular heat defense systems through starvation therapy to enhance photothermal therapy of tumors.
Asunto(s)
Respuesta al Choque Térmico , Espacio Intracelular , Nanoestructuras , Neoplasias , Espacio Intracelular/química , Estructuras Metalorgánicas/química , Supervivencia Celular , Humanos , Línea Celular Tumoral , Animales , Terapia Fototérmica , Neoplasias/terapiaRESUMEN
Herein, we report the first reactive oxygen species (ROS)-responsive dithioketal-linked covalent organic framework (COF) for synergetic chemotherapy and photodynamic therapy (PDT) of cancer. The singlet oxygen (1O2)-responsive COF dissociation and DC_AC50 drug release complement and reinforce each other to allow an efficient combination of PDT and chemotherapy.
Asunto(s)
Estructuras Metalorgánicas , Fotoquimioterapia , Línea Celular Tumoral , Terapia Combinada , Oxígeno , Fármacos Fotosensibilizantes , Especies Reactivas de Oxígeno , Oxígeno Singlete/químicaRESUMEN
Stimulus-responsive biodegradable nanocarriers with tumor-selective targeted drug delivery are critical for cancer therapy. Herein, we report for the first time a redox-responsive disulfide-linked porphyrin covalent organic framework (COF) that can be nanocrystallized by glutathione (GSH)-triggered biodegradation. After loading 5-fluorouracil (5-Fu), the generated nanoscale COF-based multifunctional nanoagent can be further effectively dissociated by endogenous GSH in tumor cells, releasing 5-Fu efficiently to achieve selective chemotherapy on tumor cells. Together with the GSH depletion-enhanced photodynamic therapy (PDT), an ideal synergistic tumor therapy for MCF-7 breast cancer via ferroptosis is achieved. In this research, the therapeutic efficacy was significantly improved in terms of enhanced combined anti-tumor efficiency and reduced side effects by responding to significant abnormalities such as high concentrations of GSH in the tumor microenvironment (TME).
RESUMEN
Herein, we report an inorganic photothermal agent, CuS- and an organic photosensitizer, BODIPY-loaded composite nanoscale COF material via a stepwise post-synthetic modification. The obtained CuS@COF-BDP can be a dual-modal therapeutic agent to highly inhibit MCF-7 tumor cell proliferation due to its efficient singlet oxygen generation and photothermal conversion abilities.
Asunto(s)
Antineoplásicos/farmacología , Compuestos de Boro/farmacología , Cobre/farmacología , Estructuras Metalorgánicas/farmacología , Fármacos Fotosensibilizantes/farmacología , Terapia Fototérmica , Antineoplásicos/síntesis química , Antineoplásicos/química , Compuestos de Boro/química , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Cobre/química , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Células MCF-7 , Estructuras Metalorgánicas/síntesis química , Estructuras Metalorgánicas/química , Estructura Molecular , Tamaño de la Partícula , Fármacos Fotosensibilizantes/síntesis química , Fármacos Fotosensibilizantes/química , Oxígeno Singlete/metabolismo , Relación Estructura-ActividadRESUMEN
Herein, we report, for the first time, a Pd6L8(NO3)5.4(ICG)6.6 (ICG = indocyanine green) cage-based hexagonal nanoplate (3) via a combined nanoprecipitation and solid-state anion-exchange approach. Nanoplate 3 possesses enhanced near-infrared (NIR) light-triggered 1O2 generation, high cellular uptake selective lysosome-targeting ability, and, consequently, excellent antineoplastic activity.
Asunto(s)
Antineoplásicos/farmacología , Estructuras Metalorgánicas/farmacología , Nanopartículas/química , Fármacos Fotosensibilizantes/farmacología , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Rayos Infrarrojos , Células MCF-7 , Estructuras Metalorgánicas/química , Estructura Molecular , Tamaño de la Partícula , Fotoquimioterapia , Fármacos Fotosensibilizantes/químicaRESUMEN
Chemodynamic therapy (CDT), which induces cell death by decomposing high levels of H2 O2 in tumor cells into highly toxic ·OH, is recognized as a promising antineoplastic approach. However, current CDT approaches are often restricted by the highly controlled and upregulated cellular antioxidant defense. To enhance ·OH-induced cellular damage by CDT, a covalent organic framework (COF)-based, ferrocene (Fc)- and glutathione peroxidase 4 (GPX4) inhibitor-loaded nanodrug, RSL3@COF-Fc (2b), is fabricated. The obtained 2b not only promotes in situ Fenton-like reactions to trigger ·OH production in cells, but also attenuates the repair mechanisms under oxidative stress via irreversible covalent GPX4 inhibition. As a result, these two approaches synergistically result in massive lipid peroxide accumulation, subsequent cell damage, and ultimately ferroptosis, while not being limited by intracellular glutathione. It is believed that this research provides a paradigm for enhancing reactive oxygen species-mediated oncotherapy through redox dyshomeostasis and may provide new insights for developing COF-based nanomedicine.
Asunto(s)
Antineoplásicos , Estructuras Metalorgánicas , Línea Celular Tumoral , Peróxido de Hidrógeno , Metalocenos , Oxidación-ReducciónRESUMEN
Chronic wound infections resulting from severe bacterial invasion have become a major medical threat worldwide. Herein, we report a large-area, homogeneous, and self-standing porphyrin-covalent organic framework (COF)-based membrane with encapsulated ibuprofen (IBU) via an in situ interfacial polymerization and impregnation approach. The obtained IBU@DhaTph-membrane exhibits highly effective antibacterial and anti-inflammatory effects via synergistic light-induced singlet oxygen (1 O2 ) generation and controllable IBU release, which is well supported by in vitro experiments. In addition, the IBU@DhaTph-membrane-based biocompatible "band-aid" type dressing is fabricated, and its excellent anti-infection and tissue remodeling activities are fully evidenced by in vivo chronic wound-healing experiments. This study may inspire and promote the fabrication of many more new types of COF-based multifunctional biomaterials for various skin injuries in clinical medicine.
Asunto(s)
Estructuras Metalorgánicas , Preparaciones Farmacéuticas , Porfirinas , Antibacterianos/farmacología , Antiinflamatorios , Porfirinas/farmacología , Cicatrización de HeridasRESUMEN
Two donor-acceptor motif fulvene-containing boron complexes were synthesized with fulvene diketonate boron difluoride (FDB) as the organic acceptor. Both difluoroboron complexes present aggregation-induced emission (AIE) properties and cell tracing function with excellent biocompatibility. And mechanochromic luminescence has been accomplished by the synthesis, isolation and characterization of BL2.
RESUMEN
Ca2+ , a ubiquitous but nuanced modulator of cellular physiology, is meticulously controlled intracellularly. However, intracellular Ca2+ regulation, such as mitochondrial Ca2+ buffering capacity, can be disrupted by 1 O2 . Thus, the intracellular Ca2+ overload, which is recognized as one of the important cell pro-death factors, can be logically achieved by the synergism of 1 O2 with exogenous Ca2+ delivery. Reported herein is a nanoscale covalent organic framework (NCOF)-based nanoagent, namely CaCO3 @COF-BODIPY-2I@GAG (4), which is embedded with CaCO3 nanoparticle (NP) and surface-decorated with BODIPY-2I as photosensitizer (PS) and glycosaminoglycan (GAG) targeting agent for CD44 receptors on digestive tract tumor cells. Under illumination, the light-triggered 1 O2 not only kills the tumor cells directly, but also leads to their mitochondrial dysfunction and Ca2+ overload. An enhanced antitumor efficiency is achieved via photodynamic therapy (PDT) and Ca2+ overload synergistic therapy.
Asunto(s)
Antineoplásicos/uso terapéutico , Compuestos de Boro/química , Carbonato de Calcio/química , Neoplasias/tratamiento farmacológico , Animales , Señalización del Calcio , Línea Celular Tumoral , Sinergismo Farmacológico , Glicosilación , Humanos , Ratones , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión , Fotoquimioterapia , Análisis Espectral/métodos , Difracción de Rayos X , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Herein, we report a microporous carbon nanomaterial that was generated from a nanoscale covalent organic framework precursor via a simple pyrolysis approach. The obtained carbon-based nanoparticles possessed a broad NIR absorption capacity and exhibited a high level of photothermal conversion ability (η = 50.6%) in the NIR-II biowindow. Its excellent PTT antitumor efficiency was fully evidenced by in vitro and in vivo experiments under 1064 nm laser irradiation.
Asunto(s)
Carbono/química , Estructuras Metalorgánicas/química , Nanoestructuras/química , Terapia Fototérmica/métodos , Espectroscopía Infrarroja Corta/métodos , Animales , Humanos , Células MCF-7 , Ratones , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión , Porosidad , Difracción de Polvo , Nanomedicina Teranóstica , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
As newly emerged crystalline porous materials, covalent organic frameworks (COFs) possess fascinating structures and some specific features such as modularity, crystallinity, porosity, stability, versatility, and biocompatibility. Besides adsorption/separation, sensing, catalysis, and energy applications, COFs have recently shown a promise in biomedical applications. This contribution provides an overview of the recent developments of COF-based medicines in cancer therapeutics, including drug delivery, photodynamic therapy (PDT), photothermal therapy (PTT), and combined therapy. Furthermore, the major challenges and developing trends in this field are also discussed. These recent developments are summarized and discussed to help encourage further contributions in this emerging and promising field.
Asunto(s)
Estructuras Metalorgánicas , Neoplasias/tratamiento farmacológico , Fotoquimioterapia/métodos , Adsorción , Catálisis , Humanos , PorosidadRESUMEN
Synergistic phototherapy combining photodynamic therapy (PDT) and photothermal therapy (PTT) based on near-infrared (NIR) dyes using a single light source offers the opportunity to treat diseases at deep locations. In this study, we reported human serum albumin (HSA)-involving tetra(butylamino)phthalocyanine (Pc)-based nanomaterials of HSA-α-Pc and HSA-ß-Pc as highly efficient dual-phototherapy agents, namely 1(4),8(11),15(18),22(25)-tetra(butylamino)phthalocyanine (α-Pc) and 2(3),9(10),16(17),23(24)-tetra(butylamino)phthalocyanine (ß-Pc). Both HSA-α-Pc and HSA-ß-Pc showed excellent photothermal effects under a single NIR (808 nm) laser irradiation due to the S 1 fluorescence emission quenching of Pcs. Compared to HSA-ß-Pc, HSA-α-Pc exhibited better singlet oxygen generation ability and its highly efficient PDT/PTT dual-phototherapy was also well evidenced via in vitro and vivo experiments under a single 808 nm laser irradiation. Overall, this approach would be viable for the fabrication of more new Pc-based metal-free nano agents for PDT/PTT synergistic phototherapy upon a single NIR light source.
RESUMEN
We demonstrate herein an effective cascade reaction for combined photodynamic and starvation therapy in treating breast tumors based on a photosensitizer and CO prodrug decorated NMOF. The PDT-induced ROS can further trigger CO release, and the high antitumor efficiency derived from both 1O2 and CO is well confirmed by in vitro assays and in vivo trials.
Asunto(s)
Compuestos de Boro/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Estructuras Metalorgánicas , Nanoestructuras , Fármacos Fotosensibilizantes/uso terapéutico , Monóxido de Carbono/química , Femenino , Humanos , Manganeso/química , Profármacos/uso terapéutico , Oxígeno Singlete/químicaRESUMEN
Despite the excellent photodynamic and photothermal properties of organic molecular photosensitizers (PSs) and photothermal agents (PTAs), such as porphyrin and naphthalocyanine, their poor water solubility severely impedes their biological applications. Covalent organic frameworks (COFs), as an emerging class of organic crystalline porous materials, possess free active end groups (bonding defects) and large inner pores, which make them an ideal type of nanocarriers for loading hydrophobic organic molecular PSs and PTAs by both bonding defect functionalization (BDF) and guest encapsulation approaches to obtain multifunctional nanomedicines for PDT/PTT combination therapy. In this work, we report a nanoscale COF (NCOF) prepared via a facile synthetic approach under ambient conditions. Furthermore, a dual-modal PDT/PTT therapeutic nanoagent, VONc@COF-Por (3), is successfully fabricated by stepwise BDF and guest encapsulation processes. The covalently grafted porphyrinic PS (Por) and the noncovalently loaded naphthalocyanine PTA (VONc) are independently responsible for the PDT and PTT functionalities of the nanoagent. Upon visible (red LED) and NIR (808 nm laser) irradiation, VONc@COF-Por (3) displayed high 1O2 generation and photothermal conversion ability (55.9%), consequently providing an excellent combined PDT/PTT therapeutic effect on inhibiting MCF-7 tumor cell proliferation and metastasis, which was well evidenced by in vitro and in vivo experiments. We believe that the results obtained herein can significantly promote the development of NCOF-based multifunctional nanomedicines for biomedical applications.
Asunto(s)
Antineoplásicos/farmacología , Estructuras Metalorgánicas/farmacología , Nanopartículas/química , Fotoquimioterapia , Fármacos Fotosensibilizantes/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Células MCF-7 , Estructuras Metalorgánicas/síntesis química , Estructuras Metalorgánicas/química , Compuestos Organometálicos/síntesis química , Compuestos Organometálicos/química , Compuestos Organometálicos/farmacología , Tamaño de la Partícula , Fármacos Fotosensibilizantes/síntesis química , Fármacos Fotosensibilizantes/química , Porosidad , Porfirinas/síntesis química , Porfirinas/química , Porfirinas/farmacología , Propiedades de SuperficieRESUMEN
Although post-synthetic modification (PSM) has been successfully applied to NMOF decoration, only a handful of PSM-based single-crystal-to-single-crystal (SCSC) examples have been reported, particularly those involving multistep MOF-based SCSC transformations. In this contribution, three new MOFs, namely, UiO-68-NCS, UiO-68-R6G and UiO-68-R6G', were prepared via the single-crystal-to-single-crystal post-synthetic modification approach. For bioimaging, nanosized UiO-68-NCS, UiO-68-R6G, and UiO-68-R6G' were also prepared. Herein, nanosized UiO-68-R6G with a rhodamine-based fluorescence switch was found to be a highly sensitive and selective fluorescent probe for the detection of Hg2+ both in vitro and in vivo.
Asunto(s)
Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Mercurio/análisis , Estructuras Metalorgánicas/química , Nanopartículas/química , Rodaminas/química , Animales , Cristalización , Femenino , Células HeLa , Humanos , Masculino , Conformación Molecular , Imagen Óptica , Pez CebraRESUMEN
As an important type of reactive oxygen species (ROS), hypochloric acid (HClO) is closely linked with our daily life, and its convenient and rapid detection is very significant and imperative. Fluorescent and visual probes are being recognized as powerful and convenient tools for detection of ROS in the environment and living organisms by visualizing and imaging. In this contribution, a new metal-organic framework-based fluorescent probe UiO-68-PT, which was generated from a phenthiazine-decorated benzimidazole bridging dicarboxyl ligand and ZrCl4 under solvothermal conditions via in situ one-pot approach, is reported. The obtained UiO-68-PT features a unique HClO and Vitamin C-triggered reversible redox process, which is accompanied by both visual and fluorescence changes. Therefore, it can be a highly sensitive, specific, and reusable sensor to detect HClO species in water via both visual and fluorogenic observation (turn-on). Furthermore, its mixed membrane material (MMM) was fabricated by the combination of UiO-68-PT and poly(vinyl alcohol), and the obtained hydrophilic MMM can be used as a reversible colorimetric card for visual detection of the HClO in aqueous solution.
RESUMEN
The lipid-derived hormone jasmonate (JA) regulates plant immunity and adaptive growth by triggering a genome-wide transcriptional programme. In Arabidopsis thaliana, JA-triggered transcriptional programming is largely orchestrated by the master transcription factor MYC2. The function of MYC2 is dependent on its physical interaction with the MED25 subunit of the Mediator transcriptional co-activator complex. Here we report the identification of JA enhancers (JAEs) through profiling the occupancy pattern of MYC2 and MED25. JA regulates the dynamic chromatin looping between JAEs and their promoters in a MED25-dependent manner, while MYC2 auto-regulates itself through JAEs. Interestingly, the JAE of the MYC2 locus (named ME2) positively regulates MYC2 expression during short-term JA responses but negatively regulates it during constant JA responses. We demonstrate that new gene editing tools open up new avenues to elucidate the in vivo function of enhancers. Our work provides a paradigm for functional study of plant enhancers in the regulation of specific physiological processes.
Asunto(s)
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Ciclopentanos/metabolismo , Proteínas Nucleares/metabolismo , Oxilipinas/metabolismo , Transducción de Señal , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Arseniato Reductasas/metabolismo , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Cromatina/metabolismo , Proteínas de Unión al ADN , Elementos de Facilitación Genéticos , Regulación de la Expresión Génica de las Plantas , Histonas/metabolismo , Regiones Promotoras Genéticas , Unión ProteicaRESUMEN
Covalent organic frameworks (COFs), an emerging class of organic porous materials, have attracted intense attention due to their versatile applications. However, the deliberate fabrication of COF-based nanomaterials for nanomedical application remains challenging due to difficulty in their size- and structure-controlled synthesis and poor aqueous dispersibility. Herein, we report two boron-dipyrromethene (BODIPY)-decorated nanoscale COFs (NCOFs), which were prepared by the Schiff-base condensation of the free end -CHO (bonding defects in COFs) on the established imine-based NCOFs with the amino-substituted organic photosensitizer BODIPY via "bonding defects functionalization" approach. Thus BODIPY has been successfully nanocrystallized via the NCOF platform, and can be used for photodynamic therapy (PDT) to treat tumors. These NCOF-based PDT agents featured nanometer size (â¼110 nm), low dark toxicity, and high phototoxicity as evidenced by in vitro and in vivo experiments. Moreover, the "bonding defects functionalization" approach might open up new avenues for the fabrication of additional COF-based platforms for biomedical treatment.