RESUMEN

In this work, manganese (Mn)-doped CuInSe quantum dots (QDs) with a ZnS passivation layer (MnCuInSe/ZnS) have been synthesized via a one-pot microwave-assisted hydrothermal reaction using glutathione (GSH) as a stabilizer. The MnCuInSe/ZnS core-shell QDs combine magnetic resonance imaging (MRI), excitation-dependent red emission, and reactive oxygen radical generation functions, in which regulation of Mn2+ incorporation leads to synergistic imaging and therapeutic modalities. The MnCuInSe/ZnS QDs exhibit high colloidal and photochemical stability in simulated media and at different pH values. An r2/r1 ratio of 9.99 was calculated from MRI studies suggesting their potential application as dual-modal imaging agents. Based on in vitro tests on Hela, B16, and HepG2 cell lines, it is apparent that MnCuInSe/ZnS QDs impose no significant cytotoxicity in the dark, while they can efficiently generate singlet oxygen radicals for photodynamic therapy of cancers, killing more than 80% of B16 cells within 5 min of laser irradiation (671 nm, 1 W cm-2). Furthermore, in vitro fluorescence imaging and cellular internalization of QDs are examined to visualize cellular uptake and in situ ROS generation. Therefore, this research exemplifies a new set of multifunctional chalcogenide QDs for theranostic applications.

Asunto(s)

Fotoquimioterapia , Puntos Cuánticos , Humanos , Manganeso , Sulfuros , Compuestos de Zinc

RESUMEN

For quantum dot sensitized solar cells (QDSSCs), modifying conservative polysulfide electrolytes with polymer additives has been proven as an effective method to control charge recombination processes at the TiO2/QDs/electrolyte interface and to accomplish efficient cell devices. In this respect, the polysulfide electrolyte is modified with polymeric and sulfur-rich graphitic carbon nitride (SGCN) to enhance the photovoltaic performance of QDSSCs. For the first time, SGCN is used to passivate surface trap states and act as the steric hindrance between TiO2/QDs/electrolyte interfaces. The QDSSCs fabricated with GCN and SGCN additives exhibited higher efficiencies, especially improved short-circuit current (JSC) and fill factors (FFs) than those of the liquid electrolyte. Cu-In-S sensitized QDSSCs constructed with GCN and SGCN additives exhibited efficiencies of 6.73% and 7.13%, respectively, whereas the liquid electrolytes delivered an efficiency of 6.16%. Additionally, the applicability of SGCN additives in various Cu-based QDSSCs to enhance their photovoltaic performance is further verified using Cu-In-Se QDSSCs. An increase in the conversion efficiencies of QDSSCs with SGCN additives is possibly due to (1) their electron-rich surface which can act as an obstacle for electron-hole recombination, thereby suppressing the back-transfer of photo-induced electrons to the QD/electrolyte interface; (2) SGCN facilitates the reduction of Sn2- to S2- redox couple, thus providing holes towards the QDs/electrolyte more efficiently. Overall, this work provides an innovative and economic additive to modify polysulfide electrolytes, thereby controlling the TiO2/QDs/electrolyte interfaces of QDSSCs.

RESUMEN

Carbon-based artificial nanoenzymes have gained increasing interest as emerging and promising nanotheranostic agents due to their biocompatibility, low cost, and straightforward production. Herein, a multifunctional Mn, N, and S incorporated carbon dots (MnNS:CDs) nanoenzyme exhibiting scavenging activity against reactive oxygen species (ROS) and reactive nitrogen species (RNS), photoluminescence quantum yield of 17.7%, and magnetic resonance imaging (MRI) contrast was explored. The optical, magnetic, and antioxidant properties of MnNS:CDs were then regulated by control over Mn incorporation to achieve higher photostability and antioxidant properties. Furthermore, conjugation of MnNS:CDs with hyaluronic acid (HA) (denoted as MnNS:CDs@HA) endowed them with high biocompatibility, which is validated by in vivo studies on zebrafish, and the ability to specifically target cluster determinant 44 (CD44)-overexpressing B16F1 cells, as verified by in vitro confocal and MRI studies. The MnNS:CDs@HA probe with therapeutic antioxidant and dual-modal imaging capability was further assessed for non-covalent binding of doxorubicin (DOX) as a model chemotherapeutic cancer drug. Results showed that targeted delivery and pH-dependent release of DOX elicited apparent cell toxicity (90%) toward B16F1 cancer cells when compared to free DOX treatment group (60%). Benefiting from their intrinsic antioxidant properties, and dual-modal imaging ability, the MnNS:CDs@HA nanocarrier is projected to improve non-invasive targeted diagnosis and therapy. STATEMENT OF SIGNIFICANCE: Carbon dots (CDs) have gained increasing interest as emerging and promising artificial functional nanomaterials that mimic the structures and functions of natural enzymes. In this work, Mn, N, and S incorporated CDs (MnNS:CDs) were synthesized using a one-pot microwave hydrothermal method to serve as fluorescent and magnetic resonance imaging probes, and catalase mimics in the reduction of the oxidative-stress related damage. Further conjugation of the probes with hyaluronic acid endows them with a good in vitro and in vivo biocompatibility as well as the capability to selectively target CD44-overexpressing cancer cells, as investigated by in vitro fluorescence, and magnetic resonance imaging. The dual-modal nanoprobe was then used to carry on doxorubicin through a non-covalent association. Favorably, targeted delivery, and pH-responsive release of doxorubicin enhanced cell killing efficiency by 50% as opposed to the free doxorubicin treatment group. The presented theranostic heteroatom doped CDs hold great promise for dual-modal imaging enabling accurate diagnosis coupled with therapeutic effect through free radical scavenging and chemotherapy.

Asunto(s)

Carbono , Puntos Cuánticos , Animales , Sistemas de Liberación de Medicamentos , Radicales Libres , Medicina de Precisión , Pez Cebra

RESUMEN

In this work, manganese-doped carbon quantum dots (Mn-CQDs) have been synthesized through a one-pot hydrothermal method by using waste green tea. The Mn2+ dopants were introduced to impart magnetic resonance capability. Upon optimization of the experimental conditions, magnetofluorescent Mn-CQDs exhibit an excitation-dependent blue emission. The abundant functional groups on Mn-CQDs not only promote water solubility but also allow straightforward functionalization with amine groups. The amine-terminated Mn-CQDs were then subsequently conjugated to folic acid (FA) and chlorin e6 (Ce6) to obtain the Mn-CQDs@FA/Ce6 magnetofluorescent photodynamic therapy (PDT) agent. in vitro studies using three different cells indicated specific targeting of Mn-CQDs@FA/Ce6 to the overexpressing folate receptor human epithelial carcinoma cell line (HeLa) cancer cells. Furthermore, Mn-CQDs@FA/Ce6 enhanced magnetic resonance imaging (MRI) signal with an r2 /r1 ratio of 5.77. Favorably, by using the Mn-CQDs@FA delivery system, active Ce6 can reach the cellular interior while its red fluorescence (FL) and reactive oxygen species generation can be retained, as has been verified by confocal microscopy. in vitro cell viability studies verified the biocompatibility of Mn-CQDs@FA/Ce6 nanohybrid with no significant toxicity up to 500 ppm while PDT treatment with 5 min irradiation (671 nm, 1 W cm-2 ) was effective in killing >90% of cells. The light-triggered Mn-CQDs@FA/Ce6 multifunctional hybrid can serve as a dual-modal FL/MRI probe and as an efficient PDT agent to detect and eradicate cancer cells remotely.

Asunto(s)

Carbono , Manganeso , Neoplasias , Imagen Óptica , Fotoquimioterapia , Puntos Cuánticos , Té/química , Carbono/química , Carbono/farmacología , Células HeLa , Células Hep G2 , Humanos , Manganeso/química , Manganeso/farmacología , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Puntos Cuánticos/química , Puntos Cuánticos/uso terapéutico

RESUMEN

Herein, we present the direct aqueous synthesis of manganese (Mn) doped CuInSe2 (Mn-CISe) quantum dots (QDs) under microwave irradiation to improve the photochemical properties of solar cells. As a result of Mn doping, the narrower bandgap energy of Mn-CISe leads to higher visible light absorption. The Mn-CISe QDs are therefore used as photosensitizers in quantum dot sensitized solar cells (QDSSCs), exhibiting enhanced performance which is dependent on Mn concentration. To the best of our knowledge, this is the first time to construct an Mn-CISe sensitized-TiO2 photoanode to boost the photovoltaic performance of QDSSCs. The incorporation of Mn into CISe increases short-circuit current, which is ascribed to the effective injection of the excited electrons from QDs into TiO2 and the consequent higher electron lifetime, likely through a newly formed Mn midgap in the CISe band structure. Compared to the undoped QDs, Mn-CISe QDSSCs show a shorter electron transport time (τt) and a longer electron recombination time (τr) which are studied by intensity-modulated photocurrent spectroscopy and intensity-modulated photovoltage spectroscopy, respectively. In fact, a combination of higher light-harvesting efficiency, slower charge recombination, and a longer electron lifetime gives rise to a maximum photovoltaic performance of 6.28%.

RESUMEN

Magnetofluorescent carbon dots (Cdots) doped with both P3+ and Mn2+ (abbreviated as PMn@Cdots) have been synthesized in an aqueous solution via a microwave-assisted pyrolysis method. In this system, a P3+ dopant was introduced to enhance the emission efficiency of the Cdots, while the presence of a Mn2+ dopant granted magnetic resonance imaging (MRI) capability. To the best of our knowledge, the present work is the first attempt to regulate red-emission and free radical scavenging of PMn@Cdots to serve as a dual-modal imaging nanoprobe and an antioxidant agent. Unlike most red-emitting Cdots, the as-prepared PMn@Cdots can be readily purified from unreacted precursors through antisolvent precipitation instead of by time-consuming purification methods. The whole synthetic procedure is rapid, facile, efficiently reproducible, and scalable. More importantly, further conjugation of the PMn@Cdots with hyaluronic acid (termed PMn@Cdots/HA) gives them good in vivo and in vitro biocompatibility as well as the capability to selectively target CD44-overexpressing cancer cells, as investigated by flow cytometry, fluorescence, and MRI. Meanwhile, PMn@Cdots exhibit antioxidant activity against multiple DPPH, hydroxyl, and superoxide radicals, which is comparable to that for ascorbic acid. Favorably, PMn@Cdots/HA showed a dose-dependent cytoprotective capability against H2O2-induced oxidative stress in B16F1, HeLa, and HEL cells. Therefore, the Cdot based theranostic platform can simultaneously function as a potential therapeutic candidate and as a dual-modal probe for enabling accurate diagnosis in future clinical applications.

RESUMEN

Multimodal therapy is an emerging medical intervention to overcome the current limitation in cancer therapy combining treatment modalities with different mechanisms of action to eradicate tumors. This study demonstrates a targeted multifunctional bovine serum albumin (BSA)-functionalized CuFeS2/chlorin e6 (Ce6) for synergistic photothermal therapy (PTT) and photodynamic therapy (PDT) effects. The CuFeS2 nanocrystals were synthesized through a simple heating-up approach and transferred into an aqueous phase using BSA in an ultrasonic-assisted microemulsion method. The as-prepared CuFeS2@BSA nanoparticles further conjugated with folic acid (FA) followed by attachment of Ce6 to form the Ce6:CuFeS2@BSA-FA nanohybrid with improved solubility and strong near-infrared (NIR) absorbance and fluorescence. It is the first report to fabricate the targeted Ce6:CuFeS2@BSA-FA hybrid and evaluates their synergistic PTT/PDT effect using a single laser. The Ce6:CuFeS2@BSA-FA hybrid showed lower toxicity in vitro (HeLa and HepG2 cells) and in vivo (zebrafish embryos), while they are selectively recognized and internalized by HeLa cells that over-express folate receptors. Compared to each modality applied separately, the combined single-laser-induced PTT and PDT treatment showed the enhanced generation of heat and reactive oxygen species (ROS) with synergistic cancer killing under 671 nm laser irradiation (10 min, 1 W/cm2). As a biocompatible targeted nanoprobe, the multifunctional nanohybrid holds promise in combined PDT/PTT synergistic therapy to achieve better efficacy.

Asunto(s)

Cobre/uso terapéutico , Receptores de Folato Anclados a GPI/antagonistas & inhibidores , Hipertermia Inducida , Compuestos de Hierro/uso terapéutico , Rayos Láser , Nanopartículas/química , Fotoquimioterapia , Fármacos Fotosensibilizantes/química , Albúmina Sérica Bovina/química , Animales , Supervivencia Celular/efectos de los fármacos , Cobre/toxicidad , Endocitosis/efectos de los fármacos , Ácido Fólico/química , Células HeLa , Células Hep G2 , Humanos , Compuestos de Hierro/toxicidad , Nanopartículas/toxicidad , Nanopartículas/ultraestructura , Aceites/química , Especies Reactivas de Oxígeno/metabolismo , Espectrometría de Fluorescencia , Pez Cebra

RESUMEN

Photo-activated therapy is a non-invasive and promising medical technology for the treatment of cancers. Herein, we present Ce6-HA-CIS phototherapeutic nanohybrids composed of Cu-In-S (CIS) heterostructured nanorod (HS-rod), chlorin e6 (Ce6), and hyaluronic acid (HA) for the use in targeted photodynamic/photothermal therapy (PDT/PTT). In the Ce6-HA-CIS nanohybrids, the CIS HS-rod was investigated as a PTT agent to convert light into thermal energy, with Ce6 acting as a PDT agent to generate singlet oxygen (1O2). HA encapsulated the surface of the CIS HS-rod and aided the hydrophobic CIS HS-rod in achieving aqueous solubility. HA also acts as a tumor-specific targeting vector of cancer cells bearing the cluster determinant 44 receptor. Under light irradiation, the fabricated Ce6-HA-CIS nanohybrids exhibited high photothermal conversion efficiency, good photo-stability, and satisfactory photodynamic activity. In vitro and in vivo experiments demonstrated that Ce6-HA-CIS showed low cytotoxicity and synergistic photodynamic and photothermal cancer cell killing effects as compared to PTT or PDT agents alone. Therefore, these phototherapeutic nanohybrids may enhance cancer therapy in future clinical applications.

Asunto(s)

Nanotubos/química , Fármacos Fotosensibilizantes/química , Animales , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/uso terapéutico , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Clorofilidas , Cobre/química , Embrión no Mamífero/efectos de los fármacos , Embrión no Mamífero/metabolismo , Femenino , Ácido Hialurónico/química , Ácido Hialurónico/farmacología , Ácido Hialurónico/uso terapéutico , Indio/química , Luz , Masculino , Melanoma Experimental/tratamiento farmacológico , Ratones , Fotoquimioterapia , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Porfirinas/química , Porfirinas/farmacología , Porfirinas/uso terapéutico , Oxígeno Singlete/química , Oxígeno Singlete/metabolismo , Azufre/química , Pez Cebra/crecimiento & desarrollo , Pez Cebra/metabolismo

RESUMEN

Multifunctional nanohybrids integrating diagnostic imaging with photodynamic or photothermal therapy in a single agent feature the next generation of on-demand nanomedicine to meet the challenges in cancer therapy. In the present study, bovine serum albumin (BSA) protein through one pot biomimetic mineralization at its metal binding site synthesized and stabilized manganese-doped copper selenide nanoparticles (Mn:CuSe) with excellent biocompatibility, near-infrared absorption, water solubility, and rich functional groups for further bioconjugation. Mn doping not only imparted the magnetic resonance imaging (MRI) function to the Mn:CuSe@BSA but also enhanced its heat generation ability. By taking advantage of BSA's extraordinary ligand binding capacity, folic acid (FA) and chlorin e6 (Ce6) were then conjugated onto the BSA corona to construct the Mn:CuSe@BSA-FA-Ce6 nanohybrid for specific targeting of overexpressed folate receptor cancer cells. The obtained theranostic agent exhibited dual MRI signal enhancement and synergistic photothermal/photodynamic therapy (PTT/PDT) effect, which was demonstrated in vitro on HeLa cells. As a consequence, dual modal therapy with 1 min PDT laser irradiation doubled cell killing efficiency compared to the single PDT treatment. Having better efficacy regarding biocompatibility and synergistic light-activation therapy, the Mn:CuSe@BSA-FA-Ce6 nanohybrid holds the promise for image-guided cancer therapy.

RESUMEN

This paper describes a simple approach to develop a multifunctional chlorin e6-hyaluronic-Fe3O4 (Ce6-HA-Fe3O4) theranostic agent. Oleylamine-coated Fe3O4 nanoparticles were prepared through a thermal decomposition route and subsequently transformed into an aqueous phase using hyaluronic acid (HA) via an ultrasonic-assisted emulsion approach. The functional terminal carboxyl groups of the HA outer layer not only promoted the water solubility of Fe3O4 NPs and their targeting ability towards the CD44 overexpressing cancer cells but also allowed straightforward coupling with Ce6. The tumor targeting ability and cellular uptake of the theranostic agent have been demonstrated by magnetic resonance imaging (MRI), confocal microscopy, and flow cytometry (FCM) studies. FCM analysis allowed us to quantify the cellular uptake behavior in response to increased Ce6-HA-Fe3O4 concentration. While no significant toxicity was observed, cell fluorescence signals increased strongly in correlation with the concentration. Analysis on the photodynamic therapeutic (PDT) efficiency tested on B16F1 cells revealed 76.7% cell death under laser irradiation for 10 min (671 nm, 1 W), which is attributed to the successful co-delivery of active Ce6 using HA-Fe3O4 nanocarriers. Taken together, these results indicate that the multifunctional platform retained and combined the original magnetic, fluorescence, and PDT performance of the components in a single remotely triggered nanotheranostic agent. We anticipate that the theranostic agent Ce6-HA-Fe3O4 can act as a promising targeted dual modal probe and a PDT agent to enhance diagnosis and treatment of cancer.

RESUMEN

A multifunctional magnetic drug delivery system was developed and explored as an efficient and less invasive technique to improve colon cancer diagnosis and therapy in mice. In this system, superparamagnetic iron oxide nanorod cores enhanced passive targeting by bandaging a magnet adjacent to the tumor site, whereas pluronic F127 shell acted as the carrier for paclitaxel. The pluronic-conjugated superparamagnetic iron oxide cores were prepared using the hydrothermal method. It was found that the initial pluronic concentration exerted a significant effect on the distribution of the diameters and lengths of the nanorods. Despite the variation in pluronic concentrations and dimensions of iron oxide products, all the samples exhibited negligible coercivity and remanence, confirming their superparamagnetic characteristics. The pluronic F127-superparamagnetic iron oxide nanocarriers were then prepared by encapsulation of nanorods into pluronic micelles and assessed for paclitaxel loading. Results showed that paclitaxel was incorporated into the core of the micelles through hydrophobic interactions, and that elevating both paclitaxel concentration and temperature increased the loading efficiency. The therapeutic effect of paclitaxel-loaded nanocarriers was then tested in in vitro and in vivo colon cancer models. Compared to docetaxel, the paclitaxel-loaded magnetic nanocarriers significantly suppressed tumor growth and improved survival time of xenograft mice. The accumulated magnetic nanocarriers inside the tumor also served as a contrast agent and enhanced magnetic resonance imaging localization and visualization of the small tumor.

Asunto(s)

Antineoplásicos , Neoplasias del Colon , Portadores de Fármacos , Nanopartículas de Magnetita , Paclitaxel , Animales , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Neoplasias del Colon/diagnóstico por imagen , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/uso terapéutico , Imagen por Resonancia Magnética , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapéutico , Ratones , Ratones Endogámicos BALB C , Nanotubos/química , Paclitaxel/química , Paclitaxel/farmacocinética , Paclitaxel/uso terapéutico , Nanomedicina Teranóstica

RESUMEN

Superparamagnetic iron oxide nanoparticles coated with polymers have shown low toxicity and chemical stability in physiological condition, thereby can be used to deliver encapsulated drugs throughout the body by external magnetic fields. In this study, magnetic nanoparticles were synthesized thorough co-precipitation method and their interaction with Pluronic F127 block copolymer as well as adsorption properties of polymer onto nanoparticles were investigated. Adsorption measurement revealed different adsorption behaviors below and above the polymer's critical micelle concentration. The Freundlich isotherm was found to better describe the adsorption behavior of Pluronic F127 onto SIONPs particles below the block copolymer critical micelle concentration. At higher concentration, the adsorbed amount is likely to diminish due to interpenetration of the adsorbed macromolecular micelles and volume-excluded effects for block copolymers. Furthermore, magnetic nanocomposites with different concentration of polymers were prepared through hydrothermal method. The crystalline structure, morphology, pore structure, and magnetic properties of magnetic nanoparticles/nanocomposites products at different pH and polymer concentration were studied. Results showed that due to the hematite impurities, magnetic nanocomposites synthesized at higher pH have lower magnetization.

Asunto(s)

Compuestos Férricos/química , Magnetismo , Nanopartículas/química , Poloxámero/química , Adsorción , Portadores de Fármacos , Concentración de Iones de Hidrógeno , Micelas , Microscopía Electrónica de Rastreo , Fotones , Polímeros/química , Presión , Difracción de Rayos X

RESUMEN

The physical and chemical properties of porous zero-valent iron nanoparticles (ZVINs) have highly been acknowledged in the decontamination of heavy metal containing wastes and groundwater. In the present work, the treatment of Cr-contaminant through adsorption onto the ZVINs has been studied. The morphology, crystal structure, and surface composition of Fe(O) nanoparticles were investigated by field emission scanning electron microscopy/energy dispersive X-ray spectroscopy (FE-SEM/EDS), transmission electron microscope (TEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS), respectively. X-ray absorption near edge structure (XANES) revealed that the Cr(VI) species reduce to Cr(III) while oxidizing the ZVINs to Fe2O3, Fe3O4 or FeO electrochemically. Furthermore, the nitrogen adsorption-desorption isotherm of the porous nanoparticles was similar to a type IV curve with an obvious mesopore-characteristic H3 hysteresis loop, whereas the sizes of mesopores were in the range of 30-50 nm. Experimentally, the efficiency for Cr(VI) removal in the range of 150-300 ppm was found to be > 99.9%. Remarkably, the reduction reaction was completed within 10 min in the absence of additional pH controls. This work also highlights the utility of X-ray absorption spectroscopy (XAS) coupled with conventional characterization methods to comprehensively study the speciation and possible reaction pathway in adsorption process.

RESUMEN

Amyloid-ß (Aß) oligomers are more likely to be the pathogenic agents of Alzheimer's disease. Development of multiple approaches in detection and clearance pathway for Aß, may eventually lead to diagnosis and treatments of AD. Following this concept, we proposed temperature-responsive magnetic drug delivery system (DDS). This system designed to enhance imaging tool and controlled drug delivery with the aid of conjugated antibodies to amyloid-derived diffusible ligands (anti-ADDLs), which can identify targeted ADDLs. The magnetic cores compose of conjugated Congo red (CR) to maghemite (Fe2O3) (CR-Fe2O3) have shown great advantage as multimodal imaging agents, while superparamagnetic Fe2O3 also possesses the hyperthermia therapy function. Pluronic F127 poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) PEO-PPO-PEO block copolymer known to be stimuli-responsive and show structure changes when subjected to external, temperature and magnetic signals. To form nanocomposites, magnetic cores coated with Pluronic and produce core/shell structure. X-ray diffraction (XRD), field-emission scanning electron microscopy (FE-SEM), and high-resolution transmission electron microscope (HR-TEM) were used to characterize as-synthesized magnetic nanocomposites (MNCs). Furthermore, Vibrating magnetometer experiments showed that MNCs have higher magnetization value than bare magnetic nanoparticles (MNPs) and are easy to conduct with an external magnetic field. The dependence of hydrodynamic size of MNCs to the temperature showed an increase in temperature corresponds to a decrease in the size. These results confirm that proposed system can be engineered and employed as smart drug delivery system for AD treatment.