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1.
Inorg Chem ; 63(17): 7770-7779, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38608286

RESUMO

Organic-inorganic hybrid phase-transition materials have attracted widespread attention in energy storage and sensor applications due to their structural adaptability and facile synthesis. However, increasing the phase-transition temperature (Tc) effectively remains a formidable challenge. In this study, we employed a strategy to regulate intermolecular interactions (different types of hydrogen bonds and other weak interactions), utilizing bismuth chloride as an inorganic framework and azetidine, 3,3-difluoro azetidine, and 3-carboxyl azetidine as organic components to synthesize three compounds with different Tc values: [C3H8N]2BiCl5 (1, 234 K), [C3H6NF2]3BiCl6 (2, 256 K), and [C4H8O2N]3BiCl6 (3, 350 K). 1 is a one-dimensional chain structure and 2 and 3 are zero-dimensional structures. Analysis of the crystal structure and the Hirshfeld surface and 2D fingerprints further suggests that the intermolecular forces are efficiently modulated. These findings emphasize the efficacy of our strategy in enhancing Tc and may facilitate further research in this area.

2.
ACS Appl Mater Interfaces ; 16(13): 15870-15878, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38520329

RESUMO

Employing transition metal catalysts (TMCs) to perform bioorthogonal activation of prodrugs and pro-fluorophores in biological systems, particularly in a conditional fashion, remains a challenge. Here, we used a mesoporous organosilica nanoscaffold (RuMSN), which localizes Ru(II) conjugates on the pore wall, enabling the biorthogonal photoreduction reactions of azide groups. Due to easily adjustable surface charges and pore diameter, this efficiently engineering RuMSN catalyst, with abundant active sites on the inner pore well, could spontaneously repel or attract substrates with different molecular sizes and charges and thus ensure selective bioorthogonal catalysis. Depending on it, engineering RuMSN nanoreactors showed fascinating application scales from conditional bioorthogonal activation of prodrugs and pro-fluorophores in either intra- or extracellular localization to performing intracellular concurrent and tandem catalysis together with natural enzymes.


Assuntos
Pró-Fármacos , Elementos de Transição , Catálise , Corantes Fluorescentes/química , Nanotecnologia
3.
Spectrochim Acta A Mol Biomol Spectrosc ; 308: 123668, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38029599

RESUMO

Second near-infrared (NIR-II,1000 âˆ¼ 1700 nm) therapeutic window presents an increased tissue penetration and elevated maximal permissible exposure in the application of photothermal therapy (PTT). However, the lack of NIR-II photothermal conversion agents (PCAs) limit their further development. In this work, we rationally designed and successfully developed three novel indolium-like heptamethine cyanine dyes (NFs) by installing N,N-diethylamino on the terminal ends of a conjugated polyene backbone and replacing the middle chlorine atom with o-mercapto benzoic acid and p-mercapto benzoic acid. Notably, NF2 with stronger rotating group encapsulated in organic nanoparticles (NF2 NPs) exhibited high photothermal conversion efficiency (PCE), which could come up to (61.3 %). Then we conducted serial experiments to further investigate PTT capability of NF2 NPs 4 T1 cell line and nude mice bearing 4 T1 tumor. As expected, the resulting NF2 NPs presented the excellent photothermal conversion ability and superb PTT effect both in vivo and in vitro. This study will inspire more work for future design and clinical applications of NIR-II therapeutic agents.


Assuntos
Nanopartículas , Neoplasias , Animais , Camundongos , Fototerapia , Camundongos Nus , Neoplasias/tratamento farmacológico , Ácido Benzoico , Linhagem Celular Tumoral
4.
J Pharm Biomed Anal ; 236: 115691, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-37703644

RESUMO

Letermovir is a cytomegalovirus inhibitor for cytomegalovirus infection a hematopoietic-cell transplantation. In the degradation test of Letermovir, five new impurities were detected at levels of ND âˆ¼ 2.21 % (by oxide, thermal or photolytic). These impurities were synthesized directly, characterized and identified by HRMS NMR spectra and X-ray crystallography. Then co-injected with commercial products to confirm their retention times in HPLC. The possible formation pathways and synthetic methods of these impurities were discussed in details. Furthermore, the toxicological properties of impurities were evaluated by ACD/Percepta 14.52.0 (Build 3525) software.

5.
Adv Healthc Mater ; 12(15): e2203080, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36745881

RESUMO

Phototherapy is considered a promising alternative to conventional tumor treatments due to its noninvasive modality and effective therapeutic effect. However, designing a photosensitizer with satisfactory therapeutic effect and high security remains a considerable challenge. Herein, a series of dimeric heptamethine cyanine photosensitizers with an aromatic diphenol linker at the meso position is developed to improve the photothermal conversion efficiency (PCE). Thanks to the extended conjugate system and high steric hindrance, the screened 26NA-NIR and 44BP-NIR exhibit high PCE (≈35%), bright near-infrared (NIR) fluorescence, excellent reactive oxygen species (ROS) generation capability, and improved photostability. Furthermore, their outstanding performance on imaging-guided PDT-PTT synergistic therapy is demonstrated by in vivo and in vitro experiments. In conclusion, this study designs a series of dimeric heptamethine cyanine photosensitizers and presents two compounds for potential clinical applications. The strategy provides a new method to design NIR photosensitizers for imaging-guided cancer treatment.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fototerapia , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Polímeros/uso terapêutico , Linhagem Celular Tumoral
6.
Dalton Trans ; 52(4): 955-961, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36597776

RESUMO

Phase change materials (PCMs) have drawn increasing attention for their promising applications in thermal switches, data communication, and energy storage. Because of the complexity of the interactions between molecules, it is still a challenge to design PCMs with a desired high phase transition temperature (Tc). In this study, a one-dimensional hybrid perovskite of (TEACCl)PbBr3 (1, TEACCl = Et3NCH2Cl) was successfully designed and synthesized with a Tc = 390 K. Disordering of TEACCl+ on the heating process is the origin of the structural phase transition of 1 from the P21/c to P63/mmc structure. It is noted that the phase transition is associated with an excellent switchable dielectric property, which indicates that 1 has the potential to be applied to sensor equipment. After calculation, 1 is an infrequent indirect bandgap semiconductor with an energy gap of 3.57 eV. Moreover, 1 exhibits strong red fluorescence under irradiation of UV light. This work will provide guidance for designing high Tc switching materials.


Assuntos
Compostos de Cálcio , Óxidos , Fluorescência , Transição de Fase
7.
Spectrochim Acta A Mol Biomol Spectrosc ; 286: 122027, 2023 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-36323089

RESUMO

Lysosome, an organelle which contains a number of hydrolases and hydrogen ions, plays a crucial role in cellular survival and apoptosis. If selectively destroy lysosomes membrane, inner hydrolases and hydrogen ions will leak and induce cell death. In this work, three lysosome-targeting fluorescent probes (HCL 1-3, heptamethine cyanine lysosomal-targeting probe) were designed, synthesized and developed for photodynamic therapy. Piperazine and N, N-dimethyl structures made HCL 1-3 have good lysosome targeting ability while Pearson's correlation coefficients reached 0.85, 0.87 and 0.78. It can be concluded from MTT test, HCL 1-3 have high photo cytotoxicity and low dark cytotoxicity from MTT test. Calcein/PI staining assays also supported cytotoxicity of HCL 1-3 under light conditions. In vivo experiments, HCL 2 accumulated in tumor and a strong fluorescence signal was observed at 12 h post injection. All results showed that our experiments provide help and new ideas for cyanine dyes in cancer treatment.


Assuntos
Fotoquimioterapia , Fotoquimioterapia/métodos , Prótons , Lisossomos/metabolismo , Corantes Fluorescentes/química , Hidrolases/análise , Hidrolases/metabolismo
8.
RSC Adv ; 12(54): 34843-34850, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36540208

RESUMO

Three novel pharmaceutical salts of cephalexin (CPX) with 2,6-dihydroxybenzoic acid (DHBA), 5-chlorosalicylic acid (CSA) and 5-sulfosalicylic acid (SSA), which were obtained and thoroughly explored by various analytical techniques, were found to be crystallized invariably in hydrated forms. It is the proton transfer from carboxylic or sulfonic counterions to the CPX molecules that results in the salt formation. Crystal structure analyses reveal that the N-H⋯O and O-H⋯O hydrogen bonding interactions among the CPX, acidic guest molecules and water molecules play a crucial role in the packing motifs of crystal stabilization. All the salts exhibit higher solubility compared with the parent drug. These salts offer an alternative way of increasing the number of solid forms for CPX, which facilitates selection of a suitable form in the context of drug formulation development for further repurposing investigations.

9.
Biomater Sci ; 10(20): 5912-5924, 2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36040793

RESUMO

The efficacy of free radical-based therapeutic strategies is severely hindered by nonspecific accumulation, premature release and glutathione (GSH) scavenging effects. Herein, a tumor microenvironment-responsive MPDA/AIPH@Cu-TA@HA (abbreviated as MACTH) nanoplatform was constructed by coating Cu2+ and tannic acid (TA) on the surface of azo initiator (AIPH)-loaded mesoporous polydopamine (MPDA) nanoparticles and further modifying them with hyaluronic acid (HA) to achieve tumor-specific photothermal/thermodynamic/chemodynamic synergistic therapy (PTT/TDT/CDT). Once accumulated and internalized into cancer cells through CD44 receptor-mediated active targeting and endocytosis, the HA shell of MACTH would be preliminarily degraded by hyaluronidase (HAase) to expose the Cu-TA metal-phenolic networks, which would further dissociate in response to an acidic lysosomal environment, leading to HAase/pH dual-responsive release of Cu2+ and AIPH. On the one hand, the released Cu2+ could deplete the overexpressed GSH via redox reactions and produce Cu+, which in turn catalyzes endogenous H2O2 into highly cytotoxic hydroxyl radicals (˙OH) for CDT. On the other hand, the local hyperthermia generated by MACTH under 808 nm laser irradiation could not only augment CDT efficacy through accelerating the Cu+-mediated Fenton-like reaction, but also trigger the decomposition of AIPH to produce biotoxic alkyl radicals (˙R) for TDT. The consumption of GSH and accumulation of oxygen-independent free radicals (˙OH/˙R) synergistically amplified intracellular oxidative stress, resulting in substantial apoptotic cell death and significant tumor growth inhibition. Collectively, this study provides a promising paradigm for customizing stimuli-responsive free radical-based nanoplatforms to achieve accurate and efficacious cancer treatment.


Assuntos
Nanopartículas , Neoplasias , Linhagem Celular Tumoral , Compostos de Diazônio , Glutationa/metabolismo , Humanos , Ácido Hialurônico/química , Hialuronoglucosaminidase , Peróxido de Hidrogênio/metabolismo , Nanopartículas/química , Neoplasias/tratamento farmacológico , Oxigênio , Piridinas , Taninos , Termodinâmica , Microambiente Tumoral
10.
J Mater Chem B ; 9(45): 9413-9422, 2021 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-34746940

RESUMO

The integration of metal-ion therapy and hydroxyl radical (˙OH)-mediated chemodynamic therapy (CDT) holds great potential for anticancer treatment with high specificity and efficiency. Herein, Ag nanoparticles (Ag NPs) were enveloped with Cu2+-based metal-organic frameworks (MOFs) and further decorated with hyaluronic acid (HA) to construct a glutathione (GSH)-activated nanoplatform (Ag@HKU-HA) for specific chemodynamic/metal-ion therapy. The obtained nanoplatform could avoid the premature leakage of Ag in circulation, but realize the release of Ag at the tumor site owing to the degradation of external MOFs triggered by Cu2+-reduced glutathione. The generated Cu+ could catalyze endogenous H2O2 to the highly toxic ˙OH by a Fenton-like reaction. Meanwhile, Ag NPs were oxidized to toxic Ag ions in the tumor environment. As expect, the effect of CDT combined with metal-ion therapy exhibited an excellent inhibition of tumor cells growth. Therefore, this nanoplatform may provide a promising strategy for on-demand site-specific cancer combination treatment.


Assuntos
Glutationa/química , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Neoplasias/terapia , Compostos Organometálicos/química , Prata , Apoptose , Transporte Biológico , Linhagem Celular , Sobrevivência Celular , Cobre , Humanos , Peróxido de Hidrogênio , Radical Hidroxila , Espécies Reativas de Oxigênio
11.
Nanoscale ; 13(37): 15677-15688, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34523626

RESUMO

Despite the great potential of cascade catalytic reactions in tumor treatment, uncontrolled catalytic activities in vivo lead to inevitable off-target toxicity to normal tissues, which greatly hampers their clinical conversion. Herein, an intelligent cascade nanoreactor (hMnO2-Au@PDA, hMAP) was constructed by depositing glucose oxidase (GOx)-mimicking ultrasmall gold nanoparticles (Au NPs) into honeycomb-shaped manganese oxide (hMnO2) nanostructures and then coating them with polydopamine (PDA) to achieve pH-responsive and photothermal-enhanced nanocatalytic therapy. Upon exposure to the mild acidic tumor microenvironment (TME), the PDA gatekeeper would collapse, and the inner hMnO2 could simultaneously deplete glutathione (GSH) and generate Mn2+, while a considerable amount of H2O2 produced from the oxidation of glucose by GOx-mimicking Au NPs could accelerate the Mn2+-mediated Fenton-like reaction, yielding sufficient highly toxic ˙OH. More importantly, the pH-responsive cascade reaction between Au NPs and hMnO2 could be further enhanced by localized hyperthermia induced from PDA under near-infrared (NIR) laser irradiation, thereby inducing significant cell apoptosis in vitro and tumor inhibition in vivo. This work provided a promising paradigm by innovatively designing a TME-responsive and photothermal-enhanced cascade catalytic nanoreactor for safe and efficient cancer therapy.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Linhagem Celular Tumoral , Ouro , Peróxido de Hidrogênio , Concentração de Íons de Hidrogênio , Indóis , Nanotecnologia , Polímeros
12.
Nano Lett ; 21(8): 3401-3409, 2021 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-33843242

RESUMO

We reported the synthesis of a tris(triazolylmethyl)amine (TTA)-bridged organosilane, functioning as Cu(I)-stabilizing ligands, and the installation of this building block into the backbone of mesoporous organosilica nanoparticles (TTASi) by a sol-gel way. Upon coordinating with Cu(I), the mesoporous CuI-TTASi, with a restricted metal active center inside the pore, functions as a molecular-sieve-typed nanoreactor to efficiently perform Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAC) reactions on small-molecule substrates but fails to work on macromolecules larger than the pore diameter. As a proof of concept, we witnessed the advantages of selective nanoreactors in screening protein substrates for small molecules. Also, the robust CuI-TTASi could be implanted into the body of animal models including zebrafish and mice as biorthogonal catalysts without apparent toxicity, extending its utilization in vivo ranging from fluorescent labeling to in situ drug synthesis.


Assuntos
Alcinos , Azidas , Animais , Catálise , Cobre , Reação de Cicloadição , Camundongos , Nanotecnologia , Peixe-Zebra
13.
Biomater Sci ; 9(3): 1020-1033, 2021 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-33325928

RESUMO

Reasonable management of the one-for-all nanoplatform can facilitate improved cancer therapy. Here, the metal-organic frameworks (MOFs) based on iron(iii) carboxylate material (MIL-101-NH2) were in situ decorated on stabilized polydopamine nanoparticles (PDANPs), which subsequently loaded glucose oxidase (GOx) via hyaluronic acid (HA) coating to structure the one-for-all intelligent core-shell nanoparticles (HG-MIL@PDANPs). Because of the inner PDANPs, the HG-MIL@PDANPs could realize near-infrared (NIR)-controllable site-specific photothermal therapy (PTT). Additionally, the core-shell nanoparticles exhibited a pH-triggered and NIR-reinforced release of Fe3+ and GOx owing to the controllable degradation of the outer shell. Hydroxyl radicals (˙OH) were produced for chemodynamic therapy (CDT) employing the Fe2+-driven Fenton reaction, which could be greatly promoted by Fe3+-involved glutathione (GSH) depletion and GOx-catalyzed acidity recovery and H2O2 self-sufficiency. Moreover, the HA ligand could enhance the tumor accumulation of the HG-MIL@PDANPs through the long blood circulation time and CD44-targeted cell recognition. The ingenious integration of PTT and CDT in one fully equipped system presented excellent synergistic antitumor efficiency in vitro and in vivo with favorable biosafety. The one-for-all intelligent core-shell nanoparticles with CD44 targeting provide a new avenue for engineering on-demand tumor-specific therapy.


Assuntos
Nanopartículas , Neoplasias , Compostos Férricos , Glucose Oxidase , Humanos , Peróxido de Hidrogênio , Neoplasias/tratamento farmacológico
14.
Colloids Surf B Biointerfaces ; 199: 111538, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33383548

RESUMO

In this study, manganese dioxide (MnO2) was attached to prussian blue (PB) by a one-pot method to prepare PBMO. Then, the GOD was loaded onto PBMO through the electrostatic interaction of hyaluronic acid (HA) to form tumor-targeted nanoplatform (PBMO-GH). Hydrogen peroxide (H2O2) and gluconic acid were produced through the GOD-catalyzed enzymatic reaction. Meanwhile, PB could not only catalyze H2O2 for oxygen generation to further promote glucose consumption but also possess the property of photothermal conversion. As a result, glucose was continuously consumed to achieve the starvation therapy (ST), and the photothermal therapy (PTT) could be realized under near-infrared (NIR) light. Besides, the Mn2+ generated by the reaction of MnO2 with glutathione (GSH) could exert Fenton-like reaction to produce highly toxic hydroxyl radicals (·OH) from H2O2, which thereby realized self-reinforcing chemodynamic therapy (CDT). In vitro and in vivo experiments demonstrated that PBMO-GH could effectively inhibit the growth of tumor cells via ST/CDT/PTT synergistic effect. Therefore, the as-prepared nanoplatform for multi-modal therapy will provide a promising paradigm for overcoming cancer.


Assuntos
Compostos de Manganês , Neoplasias , Catálise , Linhagem Celular Tumoral , Glutationa , Humanos , Peróxido de Hidrogênio , Óxidos
15.
J Mol Struct ; 1233: 130154, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-36536618

RESUMO

Bromhexine is an expectorant drug repurposing as a TMPRSS2 inhibitor, which has also been proposed for potential treatment in COVID-19 infection. Multicomponent crystal strategy has been applied in bromhexine to improve its poor solubility, which limits its bioavailability and efficacy. A new bromhexine crystal and its fumarate salt crystal have been successfully obtained by slow evaporation technique. Both compounds have been characterized by X-ray single-crystal diffraction, TGA and FT-IR spectroscopy. Hirshfeld surface analysis has been carried out to further quantify the patterns of intermolecular interactions. Compared with bromhexine, the multicomponent crystal with pharmaceutically acceptable conformer of fumaric acid shows improved thermal stability and solubility in water.

16.
Nanotechnology ; 32(3): 035102, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33002884

RESUMO

The efficiency of producing hydroxyl radicals (·OH) from hydrogen peroxide (H2O2) catalyzed by different iron compounds have been explored extensively. Exclusively, ferrocenecarboxylic acid (FCA) showed the best catalyzed activity for ·OH generation. Then, we designed and prepared near-infrared (NIR) light-responsive and folate-targeted nanoplatform, which co-delivered FCA, cisplatin and indocyanine green (ICG) for improving antitumor therapy through amplified oxidative stress. The noteworthy observation is that under the irradiation of NIR light, the lecithin structure could able to depolymerize through the photothermal conversion mechanism of encapsulated dye ICG, which has achieved an intelligent release of drugs. In addition, the released cisplatin is not only fully effective to damage the DNA of cancer cells but it is able to induce the production of intracellular H2O2, which could further be catalyzed by FCA to generate toxic ·OH for oxidative damage via Fenton and Haber-Weiss reaction. This original strategy may provide an efficient way for improved chemotherapy via amplified oxidative stress.


Assuntos
Antineoplásicos/administração & dosagem , Cisplatino/administração & dosagem , Compostos Ferrosos/administração & dosagem , Verde de Indocianina/administração & dosagem , Metalocenos/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Células A549 , Antineoplásicos/farmacologia , Cisplatino/farmacologia , Sistemas de Liberação de Medicamentos , Compostos Ferrosos/farmacologia , Ácido Fólico/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Verde de Indocianina/farmacologia , Células MCF-7 , Metalocenos/farmacologia , Nanopartículas/química , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Espécies Reativas de Oxigênio/metabolismo
17.
Small ; 16(45): e2001805, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33079449

RESUMO

The rational integration of chemotherapy and hydroxyl radical (·OH)-mediated chemodynamic therapy (CDT) holds great potential for cancer treatment. Herein, a smart biocompatible nanocatalyst based on porous core-shell cuprous oxide nanocrystals (Cu2 O-PEG (polyethylene glycol) NCs) is reported for acid-triggered chemo/chemodynamic synergistic therapy. The in situ formed high density of hydrophilic PEG outside greatly improves the stability and compatibility of NCs. The porosity of Cu2 O-PEG NCs shows the admirable capacity of doxorubicin (DOX) loading (DOX@Cu2 O-PEG NCs) and delivery. Excitingly, Cu (Cu+/2+ ) and DOX can be controllably released from DOX@Cu2 O-PEG NCs in a pH-responsive approach. The released Cu+ exerts Fenton-like catalytic activity to generate toxic ·OH from intracellular overexpressed hydrogen peroxide (H2 O2 ) for CDT via reactive oxygen species (ROS)-involved oxidative damage. Exactly, DOX can not only induce cell death for chemotherapy but also enhance CDT by self-supplying endogenous H2 O2 . After the intravenous injection, Cu2 O-PEG NCs can effectively accumulate in tumor region via passive targeting improved by external high-density PEG shell. Additionally, the effect of boosted CDT combined with chemotherapy presents excellent in vivo antitumor ability without causing distinct systemic toxicity. It is believed that this smart nanocatalyst responding to the acidity provides a novel paradigm for site-specific cancer synergetic therapy.


Assuntos
Cobre , Doxorrubicina , Linhagem Celular Tumoral , Porosidade
18.
Nanoscale ; 12(33): 17319-17331, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32789333

RESUMO

The emergence of hydroxyl radical (˙OH)-mediated chemodynamic therapy (CDT) by the Fenton or Fenton-like reaction holds great potential for improving anticancer efficacy. Herein, an activatable autocatalytic nanoreactor (HT@GOx-DMONs) was developed for self-boosting Fenton-like CDT via decorating Cu2+-based metal-organic frameworks (MOFs) on glucose oxidase (GOx)-loaded dendritic mesoporous organosilica nanoparticles (DMONs) for the first time. The obtained nanoreactor could prevent the premature leakage of Cu2+ and GOx in neutral physiological environments conducted by the gatekeeper of growing carboxylate MOF (HKUST-1), but the explosive release of agents was realized due to the activated degradation of external HKUST-1 in acidic condition of endo/lysosomes, which thereby endowed this nanoreactor with the performance of pH-triggered ˙OH generation driven by Cu+-mediated autocatalytic Fenton-like reaction. Excitingly, Cu2+-induced glutathione (GSH) depletion and GOx-catalyzed H2O2 self-sufficiency unlocked by acid dramatically enhanced ˙OH generation. As expected, the effect of self-amplified CDT based on Cu2+-containing HT@GOx-DMONs presented wonderful in vitro toxicity and in vivo antitumor ability without leading to significant side-effects. The resulting nanoreactor with GSH consumption and H2O2 self-supply activated by acid may provide a promising paradigm for on-demand CDT.


Assuntos
Glucose Oxidase , Peróxido de Hidrogênio , Glutationa , Concentração de Íons de Hidrogênio , Nanotecnologia
19.
Langmuir ; 36(23): 6345-6351, 2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-32388995

RESUMO

Cutting off the energy supply by glucose oxidase (GOx) to starve cancer cells has been a feasible and efficient oncotherapy strategy. The employment of GOx can effectively starve tumor cells by aerobic hydrolysis of glucose hopefully strengthening the abnormality (including the decrease in pH, the increase of hypoxia, and toxic hydrogen peroxide) in the tumor microenvironment (TME). On this basis, we designed and fabricated a GOx-conjugated yolk-shell Ag@mSiO2 nanoframe with Ag NPs and GOx-conjugated mesoporous silica as the yolk and the shell, respectively, to make full use of changes the GOx induces in TME. Specifically, lower pH and H2O2 could accelerate the transformation of Ag nanoparticles to poisonous Ag ions. At the same time, the anabatic hypoxia condition in turn activated chemotherapy drug tirapazamine (TPZ) to exert a chemotherapeutic effect, thereby achieving effective chemo/starvation and metal ion multimodality therapy. The drug release experiment in vitro demonstrated that the GOx is the key to the nanocarriers, which can activate the whole system. The excellent cellular uptake performances of nanocarriers were corroborated by a confocal laser scanning microscope (CLSM). In addition, its superb cancer-killing effect has been confirmed by cytotoxicity and apoptosis experiments. These results indicated that the drug-delivery system achieved the cascade cancer-killing process in situ and synergistic chemo/starvation/metal ion therapy, which has a bright prospect for treating cancer.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Preparações Farmacêuticas , Peróxido de Hidrogênio , Dióxido de Silício , Prata
20.
Langmuir ; 36(19): 5262-5270, 2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32338925

RESUMO

Dendritic mesoporous silica nanoparticles represent a new biomedical application platform due to their special central radial pore structure for the loading of drugs and functional modification. Herein, we report functionalized dendritic mesoporous organosilica nanoparticles (DMONs), a pH-triggered Fenton reaction generator (TA/Fe@GOD@DMONs), incorporating natural glucose oxidase (GOD) in the DMONs with tannic acid (TA) grafted using Fe3+ on the surface, that have been designed and constructed for efficient tumor ablation with self-supplied H2O2 and accelerated conversion of Fe3+/Fe2+ by TA. In view of the deficiency of endogenous H2O2, the self-supply through the TA/Fe@GOD@DMONs platform represented a high-yielding source of peroxygen. Furthermore, the production of Fe2+ induced by TA greatly improved the efficiency of the Fenton reaction resulting in significant tumor inhibition. This new design represents as novel paradigm for the development of autocatalytic Fenton nanosystems for effective treatment of tumors.

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