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1.
Small ; : e2401931, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38708707

RESUMO

Chemodynamic therapy (CDT) is a non-invasive strategy for generating reactive oxygen species (ROS) and is promising for cancer treatment. However, increasing ROS in tumor therapy remains challenging. Therefore, exogenous excitation and inhibition of electron-hole pair recombination are attractive for modulating ROS storms in tumors. Herein, a Ce-doped BiFeO3 (CBFO) piezoelectric sonosensitizer to modulate ROS generation and realize a synergistic mechanism of CDT/sonodynamic therapy and piezodynamic therapy (PzDT) is proposed. The mixed Fe2+ and Ce3+ can implement a circular Fenton/Fenton-like reaction in the tumor microenvironment. Abundant ·OH can be generated by ultrasound (US) stimulation to enhance CDT efficacy. As a typical piezoelectric sonosensitizer, CBFO can produce O2 - owing to the enhanced polarization by the US, resulting in the motion of charge carriers. In addition, CBFO can produce a piezoresponse irradiated upon US, which accelerates the migration rate of electrons/holes in opposite directions and results in energy band bending, further achieving toxic ROS production and realizing PzDT. Density functional theory calculations confirmed that Ce doping shortens the diffusion of electrons and improves the conductivity and catalytic activity of CBFO. This distinct US-enhanced strategy emphasizes the effects of doping engineering and piezoelectric-optimized therapy and shows great potential for the treatment of malignant tumors.

2.
Small ; 19(45): e2303057, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37434100

RESUMO

Ferroptosis, as a non-apoptotic cell death pathway, has attracted increasing attention for cancer therapy. However, the clinical application of ferroptosis-participated modalities is severely limited by the low efficiency owing to the intrinsic intracellular regulation pathways. Herein, chlorin e6 (Ce6) and N-acetyl-l-cysteine-conjugated bovine serum albumin-ruthenium dioxide is elaborately designed and constructed for ultrasound-triggered peroxynitrite-mediated ferroptosis. Upon ultrasound stimulation, the sonosensitizers of Ce6 and RuO2 exhibit highly efficient singlet oxygen (1 O2 ) generation capacity, which is sequentially amplified by superoxide dismutase and catalase-mimicking activity of RuO2 with hypoxia relief. Meanwhile, the S-nitrosothiol group in BCNR breaks off to release nitric oxide (NO) on-demand, which then reacts with 1 O2 forming highly cytotoxic peroxynitrite (ONOO- ) spontaneously. Importantly, BCNR nanozyme with glutathione peroxidase-mimicking activity can consume glutathione (GSH), along with the generated ONOO- downregulates glutathione reductase, avoiding GSH regeneration. The two-parallel approach ensures complete depletion of GSH within the tumor, resulting in the boosted ferroptosis sensitization of cancer cells. Thus, this work presents a superior paradigm for designing peroxynitrite-boosted ferroptosis sensitization cancer therapeutic.


Assuntos
Antineoplásicos , Ferroptose , Neoplasias , Humanos , Ácido Peroxinitroso/farmacologia , Antineoplásicos/farmacologia , Ultrassonografia , Óxido Nítrico/metabolismo , Glutationa/metabolismo , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo
3.
Adv Mater ; 35(38): e2304262, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37437264

RESUMO

Piezocatalytic therapy, which generates reactive oxygen species (ROS) under mechanical force, has garnered extensive attention for its use in cancer therapy owing to its deep tissue penetration depth and less O2 -dependence. However, the piezocatalytic therapeutic efficiency is limited owing to the poor piezoresponse, low separation of electron-hole pairs, and complicated tumor microenvironment (TME). Herein, a biodegradable, porous Mn-doped ZnO (Mn-ZnO) nanocluster with enhanced piezoelectric effect is constructed via doping engineering. Mn-doping not only induces lattice distortion to increase polarization but also creates rich oxygen vacancies (OV ) for suppressing the recombination of electron-hole pairs, leading to high-efficiency generation of ROS under ultrasound irradiation. Moreover, Mn-doped ZnO shows TME-responsive multienzyme-mimicking activity and glutathione (GSH) depletion ability owing to the mixed valence of Mn (II/III), further aggravating oxidative stress. Density functional theory calculations show that Mn-doping can improve the piezocatalytic performance and enzyme activity of Mn-ZnO due to the presence of OV . Benefiting from the boosting of ROS generation and GSH depletion ability, Mn-ZnO can significantly accelerate the accumulation of lipid peroxide and inactivate glutathione peroxidase 4 (GPX4) to induce ferroptosis. The work may provide new guidance for exploring novel piezoelectric sonosensitizers for tumor therapy.


Assuntos
Ferroptose , Neoplasias , Óxido de Zinco , Humanos , Espécies Reativas de Oxigênio , Eletrônica , Elétrons , Glutationa , Oxigênio , Neoplasias/tratamento farmacológico , Microambiente Tumoral
4.
Adv Mater ; 35(29): e2300648, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37058740

RESUMO

Piezocatalytic therapy is a new-emerging reactive oxygen species (ROS)-enabled therapeutic strategy that relies on built-in electric field and energy-band bending of piezoelectric materials activated by ultrasound (US) irradiation. Despite becoming a hot topic, material development and mechanism exploration are still underway. Herein, as-synthesized oxygen-vacancy-rich BiO2- x nanosheets (NSs) demonstrate outstanding piezoelectric properties. Under US, a piezo-potential of 0.25 V for BiO2- x NSs is sufficient to tilt the conduction band to be more negative than the redox potentials of O2 /• O2 - , • O2 - /H2 O2 , and H2 O2 /• OH, which initiates a cascade reaction for ROS generation. Moreover, the BiO2- x NSs exhibit peroxidase and oxidase-like activities to augment ROS production, especially in the H2 O2 -overexpressed tumor microenvironment. Density functional theory calculations show that the generated oxygen vacancies in BiO2- x NSs are favorable for H2 O2  adsorption and increasing the carrier density to produce ROS. Furthermore, the quick movement of electrons enables an excellent sonothermal effect, for example, rapid rise in temperature to nearly 65 °C upon US with low power (1.2 W cm-2 ) and short time (96 s). Therefore, this system realizes a multimode synergistic combination of piezocatalytic, enzymatic, and sonothermal therapies, providing a new direction for defect engineering-optimized piezoelectric materials for tumor therapy.


Assuntos
Corantes , Oxigênio , Espécies Reativas de Oxigênio , Adsorção , Eletricidade
5.
ACS Nano ; 16(12): 20805-20819, 2022 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-36378717

RESUMO

The emergence of X-ray-induced photodynamic therapy (X-PDT) holds tremendous promise for clinical deep-penetrating cancer therapy. However, the clinical application of X-PDT in cancer treatment is still limited due to the hypoxic property of cancerous tissue, the inherent antioxidant system of tumor cells, and the difficulty in matching the absorption spectra of photosensitizers. Herein, a versatile core-shell radiosensitizer (SCNPs@DMSN@CeOx-PEG, denoted as SSCP) was elaborately designed and constructed to enhance X-PDT by coating tunable mesoporous silica on nanoscintillators, followed by embedding the cerium oxide nanoparticles in situ. The obtained SSCP radiosensitizer demonstrated a distinct blue-shift in the ultraviolet light region, so that it could perfectly absorb the ultraviolet light converted by the SCNPs core, resulting in the formation of photoinduced electron-hole (e--h+) pairs separation to generate reactive oxygen species (ROS). In addition, the cerium oxide exhibits high glutathione consumption to heighten ROS accumulation, and catalase-like activity to alleviate the hypoxia, which further enhances the efficiency of radiotherapy. Benefiting from the abundant Lu and Ce elements, the computed tomography imaging performance of SSCP is about 3.79-fold that of the clinical contrast agent (iohexol), which has great potential in both preclinical imaging and clinical translation.


Assuntos
Cério , Nanopartículas , Fotoquimioterapia , Humanos , Fotoquimioterapia/métodos , Raios X , Espécies Reativas de Oxigênio , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Hipóxia/tratamento farmacológico , Linhagem Celular Tumoral
6.
Nano Lett ; 22(15): 6409-6417, 2022 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-35867897

RESUMO

The development of a manageable reactive nitrogen species-potentiated nitrosative stress induction system for cancer therapy has remained elusive. Herein, tailored silica-based nanoscintillators were reported for low-dosage X-ray boosting for the in situ formation of highly cytotoxic peroxynitrite (ONOO-). Significantly, cellular nitrosative stress revolving around the intracellular protein tyrosine nitration through ONOO- pathways was explored. High-energy X-rays were directly deposited on silica-based nanoscintillators, forming the concept of an open source and a reduced expenditure-aggravated DNA damage strategy. Moreover, the resultant ONOO-, along with the released nitric oxide, not only can act as "oxygen suppliers" to combat tumor hypoxia but also can induce mitochondrial damage to initiate caspase-mediated apoptosis, further improving the therapeutic efficacy of radiotherapy. Thus, the design of advanced nanoscintillators with specific enhanced nitrosative stress offers promising potential for postoperative radiotherapy of colon cancer.


Assuntos
Neoplasias do Colo , Ácido Peroxinitroso , Neoplasias do Colo/radioterapia , Humanos , Óxido Nítrico/metabolismo , Estresse Nitrosativo , Ácido Peroxinitroso/metabolismo , Espécies Reativas de Nitrogênio/metabolismo , Dióxido de Silício
7.
ACS Nano ; 16(6): 8939-8953, 2022 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-35666853

RESUMO

Nanosystem-mediated tumor radiosensitization strategy combining the features of X-ray with infinite penetration depth and high atomic number elements shows considerable application potential in clinical cancer therapy. However, it is difficult to achieve satisfactory anticancer efficacy using clinical radiotherapy for the majority of solid tumors due to the restrictions brought about by the tumor hypoxia, insufficient DNA damage, and rapid DNA repair during and after treatment. Inspired by the complementary advantages of nitric oxide (NO) and X-ray-induced photodynamic therapy, we herein report a two-dimensional nanoplatform by the integration of the NO donor-modified LiYF4:Ce scintillator and graphitic carbon nitride nanosheets for on-demand generation of highly cytotoxic peroxynitrite (ONOO-). By simply adjusting the Ce3+ doping content, the obtained nanoscintillator can realize high radioluminescence, activating photosensitive materials to simultaneously generate NO and superoxide radical for the formation of ONOO- in the tumor. Obtained ONOO- effectively amplifies therapeutic efficacy of radiotherapy by directly inducing mitochondrial and DNA damage, overcoming hypoxia-associated radiation resistance. The level of glutamine synthetase (GS) is downregulated by ONOO-, and the inhibition of GS delays DNA damage repair, further enhancing radiosensitivity. This work establishes a combinatorial strategy of ONOO- to overcome the major limitations of radiotherapy and provides insightful guidance to clinical radiotherapy.


Assuntos
Neoplasias , Ácido Peroxinitroso , Humanos , Óxido Nítrico , Dano ao DNA , Reparo do DNA , Neoplasias/radioterapia
8.
Small ; 18(28): e2200786, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35661402

RESUMO

Mild photothermal therapy (PTT, <45 °C) can prevent tumor metastasis and heat damage to normal tissue, compared with traditional PTT (>50 °C). However, its therapeutic efficacy is limited owing to the hypoxic tumor environment and tumor thermoresistance owing to the overproduction of heat shock proteins (HSPs). Herein, a near-infrared (NIR)-triggered theranostic nanoplatform (GA-PB@MONs@LA) is designed for synergistic mild PTT and enhanced Fenton nanocatalytic therapy against hypoxic tumors. The nanoplatform is fabricated by the confined formation of Prussian blue (PB) nanoparticles in mesoporous organosilica nanoparticles (MONs), followed by the loading of gambogic acid (GA), an HSP90 inhibitor, and coating with thermo-sensitive lauric acid (LA). Upon NIR irradiation, the photothermal effect (44 °C) of PB not only induces apoptosis of tumor cells but also triggers the on-demand release of GA, inhibiting the production of HSP90. Moreover, the delivered heat simultaneously enhances the catalase-like and Fenton activity of PB@MONs@LA in an acidic tumor microenvironment, relieving the tumor hypoxia and promoting the generation of highly toxic •OH. In addition, the nanoplatform enables magnetic resonance/photoacoustic dual-modal imaging. Thus, this study describes a distinctive paradigm for the development of NIR-triggered theranostic nanoplatforms for enhanced cancer therapy.


Assuntos
Antineoplásicos , Hipertermia Induzida , Nanopartículas , Neoplasias , Linhagem Celular Tumoral , Preparações de Ação Retardada , Humanos , Hipertermia Induzida/métodos , Hipóxia/terapia , Neoplasias/terapia , Fototerapia/métodos , Medicina de Precisão , Nanomedicina Teranóstica/métodos , Microambiente Tumoral
9.
Adv Mater ; 34(7): e2107054, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34865269

RESUMO

Clinical applications of nanozyme-initiated chemodynamic therapy (NCDT) have been severely limited by the poor catalytic efficiency of nanozymes, insufficient endogenous hydrogen peroxide (H2 O2 ) content, and its off-target consumption. Herein, the authors developed a hollow mesoporous Mn/Zr-co-doped CeO2 tandem nanozyme (PHMZCO-AT) with regulated multi-enzymatic activities, that is, the enhancement of superoxide dismutase (SOD)-like and peroxidase (POD)-like activities and inhibition of catalase (CAT)-like activity. PHMZCO-AT as a H2 O2 homeostasis disruptor promotes H2 O2 evolution and restrains off-target elimination of H2 O2 to achieve intensive NCDT. PHMZCO-AT with SOD-like activity catalyzes endogenous superoxide anion (O2 •- ) into H2 O2 in the tumor region. The suppression of CAT activity and depletion of glutathione by PHMZCO-AT largely weaken the off-target decomposition of H2 O2 to H2 O. Elevated H2 O2 is then catalyzed by the downstream POD-like activity of PHMZCO-AT to generate toxic hydroxyl radicals, further inducing tumor apoptosis and death. T1 -weighted magnetic resonance imaging and X-ray computed tomography imaging are also achieved using PHMZCO-AT due to the existence of paramagnetic Mn2+ and the high X-ray attenuation ability of elemental Zr, permitting in vivo tracking of the therapeutic process. This work presents a typical paradigm to achieve intensive NCDT efficacy by regulating multi-enzymatic activities of nanozymes to perturb the H2 O2 homeostasis.


Assuntos
Cério , Neoplasias , Catálise , Humanos , Peróxido de Hidrogênio/uso terapêutico , Radical Hidroxila , Neoplasias/tratamento farmacológico
10.
Spectrochim Acta A Mol Biomol Spectrosc ; 246: 118964, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32992240

RESUMO

Colorimetric and fluorescent detection of F- have attracted enormous interest owing to their simplicity, low-cost and high selectivity. However, traditional colorimetric and fluorescent sensors mainly based on the insoluble and toxic organic molecules, which is not favorable for sensing F- in water media and living cells. In this work, we designed fluorescent carbon dots (CDs) with excellent water solubility and good biocompatibility as a colorimetric and fluorescent dual-model probe for the detection of F-. The CDs were prepared by a green, one-step hydrothermal strategy from wheat straw without any additives and surface passivation. The obtained CDs exhibited a bright blue fluorescence, special response to F- and low cytotoxicity. More interestingly, a significant color change from light yellow to red can be observed by the naked eye upon addition of F- ions to the CDs solution probably due to the formation of hydrogen bonding between CDs and F-. Besides, the fluorescence of CDs also can be selectively quenched by F- with the detection limit of about 49 µM. Additionally, the CDs are also applied to intracellular imaging and sensing of F- in living cells. This strategy may provide a new method for the detection of F- in water media and biological systems.


Assuntos
Carbono , Pontos Quânticos , Colorimetria , Corantes Fluorescentes , Fluoretos , Pontos Quânticos/toxicidade , Triticum
11.
Nanoscale ; 12(47): 24146-24161, 2020 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-33242048

RESUMO

Gasotransmitters with high therapeutic efficacy and biosafety have been drawing the attention of researchers. Nevertheless, how to effectively deliver gases to and precisely control their generation at the lesion as well as integrate them with other therapies to realize precision therapy have remained elusive. Herein, we report a versatile Cu2+-initiated nitric oxide (NO) nanocomposite for multimodal imaging-guided synergistic chemodynamic/photodynamic/gas therapy. After the nanomedicine was ingested by tumor cells, the acidic tumor microenvironment accelerated the decomposition of CuO2 and simultaneously triggered the Fenton-like catalytic reaction of Cu2+ and H2O2 to produce highly toxic ˙OH. By virtue of the NO generation and glutathione depletion, UMNOCC-PEG can relieve the antioxidant capacity and hypoxia of the tumor to improve the efficiency of chemodynamic therapy (CDT) and photodynamic therapy (PDT). Importantly, NO and reactive oxygen species (ROS) can generate reactive nitrogen species (RNS), which can result in DNA damage, further improving the therapeutic effect (cell apoptosis rate up to 93.4%). Moreover, the inherent properties of lanthanide ions endow UMNOCC-PEG with upconversion luminescence (UCL), CT and MRI trimodal imaging capability, achieving precise cancer treatment. By taking advantage of these features, the strategy developed here may provide a promising application foreground to conquer malignant tumors.


Assuntos
Nanocompostos , Fotoquimioterapia , Gases , Peróxido de Hidrogênio , Medicina de Precisão , Dióxido de Silício , Nanomedicina Teranóstica
12.
Mikrochim Acta ; 187(7): 382, 2020 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-32529294

RESUMO

Fully porous silica microspheres (FPSM) with high specific surface area and hierarchical pore as matrix for HPLC were prepared. First, the porous silica nanospheres with controllable particle size and pore diameter were successfully synthesized using a dual-templating approach, the pore size of nanospheres can be increased to 18.4 nm by changing the molar ratios of octyltrimethylammonium bromide (TOMAB) and cetyltrimethyl ammonium bromide (CTAB), which is suitable for separation and analysis of biomolecules without pore enlargement. Then, the micron FPSM with hierarchical pore were synthesized by polymerization-induced colloid aggregation (PICA) using the porous nanospheres as a silicon source, which has a large mesoporous structure (35.2 nm) and high specific surface area (560 m2 g-1). Subsequently, the FPSM modified with octadecyltrichlorosilane were studied as stationary phase for separation of cytochrome C, lysozyme, ribonuclease A, and ovalbumin, bovine serum albumin, and the baseline separation of five proteins was achieved within 1 min. The prepared column was also applied to the fast separation of digests of ovalbumin, and more chromatographic peaks were obtained compared to a commercial column under the same gradient elution conditions. In addition, the static-binding capacity of the functionalized FPSM for bovine serum albumin (BSA) was measured to be 276 mg g-1, which was nearly twice the static adsorption given in literature. Therefore, these FPSM with high specific surface area and hierarchical pore structure are expected to have great potential for the separation of complex biological samples using HPLC. Graphical abstract A synthetic strategy was provided towards FPSM with hierarchical pores and high specific surface area using porous nanospheres as silicon source. The outstanding performance of the FPSM is that it has a high specific surface area while maintaining a large mesoporous size, which overcomes the disadvantage of sacrificing the specific surface area when increasing the pore size of porous silica microspheres prepared by using the traditional PICA method.


Assuntos
Microesferas , Fragmentos de Peptídeos/isolamento & purificação , Proteínas/isolamento & purificação , Dióxido de Silício/química , Adsorção , Animais , Bovinos , Cromatografia Líquida de Alta Pressão , Fragmentos de Peptídeos/química , Porosidade , Proteínas/química , Dióxido de Silício/síntese química , Extração em Fase Sólida
13.
Artigo em Inglês | MEDLINE | ID: mdl-30081269

RESUMO

Nitrogen-doped carbon dots (N-CDs) with well-distribution size and strong blue emission were successfully synthesized via a simple mild hydrothermal strategy using citric acid and ethylenediamine as co-precursors. The highly fluorescent N-CDs exhibit high fluorescence quantum yield (QY, 58.6%), excitation-independent emission behavior, and good photostability. The experimental results showed that the N-CDs can be served as a fluorescent sensing platform for detection of Cr(VI) ions due to the effective fluorescence quenching effect of Cr(VI) ions. The quenching mechanism probably arises from the inner filter effect (IFE) and the electron transfer due to the strong interactions between functional groups (COOH, OH and NH2 groups) of the N-CDs and Cr(VI) ions. It is also found that the N-CDs showed high sensitivity toward Cr(VI) ions with a detection limit of 0.26 µM. Moreover, the obtained N-CD can be employed as chemsensor to detect Cr (VI) in real river water samples, which have potential applications in the environmental water.

14.
Inorg Chem ; 57(14): 8662-8672, 2018 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-29939723

RESUMO

Highly fluorescent nanomaterials have shown great potential application in optics area. However, further improving their fluorescence properties especially for nanomaterials still remains a challenge. Specifically, luminescence of lanthanide (Ln) ions doped two-dimensional (2D) nanosheets is seldom studied. Herein, MgWO4:Ln3+ (Ln = Eu, Tb) nanosheets were successfully synthesized via a simple hydrothermal method, and the luminescence properties of these nanosheets are obviously improved through incorporation of fluorescent carbon dots (CDs) onto the surface of MgWO4:Ln3+ (CDs@MgWO4:Ln3+) nanosheets. The obtained MgWO4:Ln3+ samples have a 2D nanosheet morphology with triclinic phase, and the morphology and phase structure can be maintained after incorporating CDs onto the nanosheets' surface. Under the excitation of UV light, the obtained MgWO4:Ln3+ nanosheets exhibit the characteristic emission of the doping ions, and the emission intensity of CDs@MgWO4:Eu3+ and CDs@MgWO4:Tb3+ nanosheets increases 2- and 7-fold compared to the corresponding samples without incorporation of CDs, respectively. This luminescent enhancement mechanism might be due to the capturing electrons by CDs and energy transfer from CDs to luminescent Ln3+. The fluorescence enhancement through incorporation of CDs provides a simple and environment-friendly strategy for further improving luminescence property of other lanthanide ions doped nanomaterials.

15.
Dalton Trans ; 47(26): 8611-8618, 2018 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-29423481

RESUMO

Lanthanide ion (Yb3+, Er3+) co-doped AWO4 (A = Ca, Sr, Ba) up-conversion (UC) luminescent materials have been synthesized using a hydrothermal method and characterized by various microstructural and optical techniques. The results indicate that AWO4:Yb3+,Er3+ samples have an identical body-centered tetragonal scheelite structure with different morphologies, including CaWO4:Yb3+,Er3+ microspheres, dumbbell-like SrWO4:Yb3+,Er3+ and bipyramid-like BaWO4:Yb3+,Er3+. These samples exhibit visible emissions via an UC process under near-infrared (NIR) light (980 nm) excitation. Interestingly, the UC luminescence properties of AWO4:Yb3+,Er3+ can be prominently increased after combination with fluorescent carbon dots (CDs) to form CDs@AWO4:Yb3+,Er3+ composites. Compared to the corresponding samples without combination with CDs, the UC emission intensities of CDs@CaWO4:Yb3+,Er3+, CDs@SrWO4:Yb3+,Er3+ and CDs@BaWO4:Yb3+,Er3+ composites increase about three, six and seven fold in the green emission area, and two, three and four fold in the red emission area, respectively. The mechanism of UC luminescence enhancement is probably that the loss of non-radiative transitions from the higher energy levels to the lower excited levels could be effectively reduced through the energy capture by the CD energy levels. The fluorescence enhancement for Yb3+ and Er3+ co-doped AWO4 through combination with CDs provides a simple strategy for the tungstate system and other UC luminescent host systems.

16.
Colloids Surf B Biointerfaces ; 154: 287-296, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28351801

RESUMO

Oral chemotherapy is the preferred route for cancer treatment because it can improve the efficacy and decrease the side effects. Unfortunately, most anticancer drugs suffered from their poor oral bioavailability. Herein, we construct a novel pH-triggered oral drug delivery system by capping of mesoporous silica SBA-15 with pH-responsive polymer poly (acrylic acid) (PAA) via a facile graft-onto strategy. The experiment results demonstrated that the PAA brushes were anchored on the pore outlets of mesoporous silica SBA-15, which can be acted as the gatekeeper to control the drug molecules transport in and out of the pore channels. The PAA capped mesoporous SBA-15 (PAA/SBA-15) exhibited a high drug loading capacity (785.7mg/g), excellent pH-sensitivity and good biocompatibility. In gastric environment (pH=2.0), the drug doxorubicin (DOX) molecules were encapsulated in the pore channels because the pore outlets were capped with collapsed PAA. In contrast, in colonic environment (pH=7.6), it exhibited a fast release because of the removal of capping. In addition, the water solubility of DOX in colonic environment was enhanced after DOX being loaded into the pores of PAA/SBA-15. This pH-triggered oral drug delivery system has promising applications for treatment of colon cancer and other colon diseases.


Assuntos
Resinas Acrílicas/química , Antibióticos Antineoplásicos/metabolismo , Doxorrubicina/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Dióxido de Silício/química , Administração Oral , Antibióticos Antineoplásicos/química , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Doxorrubicina/química , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Humanos , Concentração de Íons de Hidrogênio , Cinética , Células-Tronco Mesenquimais , Nanopartículas/administração & dosagem , Nanopartículas/ultraestrutura , Porosidade
17.
J Nanosci Nanotechnol ; 16(4): 4029-34, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27451761

RESUMO

Rare earth ions (Tb3+, Eu3+) doped CaWO4 microstructures were synthesized by a facile hydrothermal route without using any templates and characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and photoluminescence (PL) spectrum. The results indicate that the asprepared samples are well crystallized with scheelite structure of CaWO4, and the average diameter of the microstructures is 2~4 µm. The morphology of CaWO4:Eu3+ microstructures can be controllably changed from microspheres to microflowers through altering the doping concentration of Eul+ from 3% to 35%, and the microflowers are constructed by a number of CaWO4:Eu3+ nanoflakes. Under the excitation of UV light, the emission spectrum of CaWO4:Eu3+ is composed of the characteristics emission of Eu3+ 5D0-7FJ (J = 1, 2, 3, 4) transitions, and that of CaWO4:Tb3+ is composed of Tb3+ 5D4-7FJ (J= 6, 5, 4, 3) transitions. Both of the optimal doping concentrations of Tb3+ and Eu3+ in CaWO4 microstructures are about 5%.

18.
Sci Rep ; 6: 21335, 2016 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-26891778

RESUMO

Colon-targeted drug delivery system has attracted much interest because it can improve therapeutic efficacy and reduce the side effect in practical clinic. Herein, we constructed a multifunctional drug delivery system with colonic targeting and tracking by up-conversion (UC) luminescence based on core-shell structured NaYF4:Yb(3+)/Er(3+)@SiO2@PMAA nanocomposite. The resultant materials exhibited bright UC luminescence, pH-responsive property and excellent biocompatibility. The drug release behaviors in different pH environment were investigated using 5-aminosalicylic acid (5-ASA) as a model drug. The 5-ASA molecules release from NaYF4:Yb(3+)/Er(3+)@SiO2@PMAA nanocomposite exhibit a significant pH-responsive colon targeted property, i.e., a little amount of drug release in simulated gastric fluid (SGF, pH = 1.2) but a large amount of drug release in simulated colonic fluid (SCF, pH = 7.4) Moreover, the drug release process could be monitored by the change of UC emission intensity. These results implied that the multifunctional nanocomposite is a promising drug carrier for targeted release of 5-ASA in the colon.


Assuntos
Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Érbio/química , Nanocompostos/química , Dióxido de Silício/química , Itérbio/química , Ácidos Aminossalicílicos/administração & dosagem , Sobrevivência Celular , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio , Cinética , Luminescência , Nanocompostos/toxicidade , Nanocompostos/ultraestrutura , Espectroscopia de Infravermelho com Transformada de Fourier , Fatores de Tempo
19.
J Nanosci Nanotechnol ; 11(3): 1871-9, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21449323

RESUMO

Thermo-sensitive nanocomposites based on mesoporous silica SBA-15 and poly(N-isopropylacrylamide) (PNIPAAm) have been synthesized via in situ radical polymerization in mesopores. The resultant materials were used as carriers to construct temperature-responsive controlled drug delivery systems. Loading of model drug ibuprofen (IBU) was ascertained by IR and UV-vis/DRS spectroscopy, and the mesostructure and pore properties of the delivery system were characterized by small-angle XRD and N2 adsorption-desorption experiment. Study on drug uptake indicated that higher polymer content in the composite, higher IBU concentration in loading solution and lower loading temperature below the lower critical solution temperature (LCST) could increase the loading amount of IBU by means of interaction between IBU and polymer and trap effect of the polymer chains in pores. Different from the uptake of IBU, however, the release of drug followed a positive temperature-responsive manner, that is, the release was accelerated upon heating above the LCST, while decelerated and lasted for a longer period of time below the LCST. This feature allows the material to function as a reversible fast/slow transition switch or rate regulator responsive to environmental temperature and to be potentially interesting in controlled delivery and other smart application fields.


Assuntos
Acrilamidas/química , Preparações de Ação Retardada/química , Ibuprofeno/química , Polímeros/química , Dióxido de Silício/química , Absorção , Resinas Acrílicas , Analgésicos não Narcóticos/administração & dosagem , Analgésicos não Narcóticos/química , Difusão , Ibuprofeno/administração & dosagem , Temperatura
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