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1.
Gen Physiol Biophys ; 43(1): 57-71, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38312035

RESUMO

The most prevalent cause of lung cancer is smoking tobacco, but exposure to second hand smoke, air pollution, and certain chemicals and substances at work can also raise the risk of disease. In this study, we scrutinized the chemoprotective effect of the metformin and atorvastatin combination against benzo[a]pyrene (BaP)-induced lung cancer in mice of Swiss albino. BaP (50 mg/kg) was used for induction of lung cancer and mice were treated with metformin, atorvastatin or their combination. Metformin + atorvastatin combination significantly (p< 0.001) improved the body weight, liver weight, suppressed the lung weight and tumor incidence and altered the levels of immunocompetent cells, polyamines, lung tumor markers, lung parameters and antioxidant parameters, respectively. Metformin + atorvastatin combination also suppressed cytokines levels, inflammatory parameters and caspase parameters. On the basis of the results, we can conclude that metformin + atorvastatin combination remarkably suppressed lung cancer via the inflammatory pathway.


Assuntos
Neoplasias Pulmonares , Metformina , Camundongos , Animais , Metformina/efeitos adversos , Metformina/metabolismo , Atorvastatina/efeitos adversos , Atorvastatina/metabolismo , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Benzo(a)pireno/toxicidade , Benzo(a)pireno/metabolismo , Transdução de Sinais , Pulmão/patologia
2.
Angew Chem Int Ed Engl ; : e202409849, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39101665

RESUMO

Transition metal catalysts (TMCs) mediated bioorthogonal catalysis expand the chemical possibilities within cells. Developing synthetic TMCs tools that emulate the efficiency and specificity of natural metalloenzymes is a rewarding yet challenging endeavor. Here, we highlight the potential of molecularly imprinted enzyme mimics (MIEs) containing a Cu center and specific substrate binding domain, for conducing dimethylpropargyloxycarbonyl (DmProc) cleavage reactions within cells. Our studies reveal that the Cu-MIEs act as highly specific guides, precisely catalyzing target substrates, even in glutathione (GSH)-rich cellular environments. By adapting templates similar to the target substrates, we evolved Cu-MIEs activity to a high level and provided a method to broaden its scope to other unique substrates. This system was applied to a thyroid hormone (T3)-responsive gene switch model, inducing firefly luciferase expression by T3 in cells. This approach verifies that MIEs effectively rescue DmProc-bearing T3 prodrugs and seamlessly integrating themself into cellular biocatalytic networks.

3.
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
4.
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.

5.
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
6.
Mol Pharm ; 16(12): 4929-4939, 2019 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-31661289

RESUMO

Breaking the threshold of intracellular reactive oxygen species (ROS) levels can cause nonspecific oxidative damage to proteins and lead to the Fenton reaction-mediated exogenous ROS production to be a new promising anticancer strategy. However, the problems, including the inefficient transport of metal catalysts and insufficient endogenous hydrogen peroxide (H2O2) content in cells, still need to be improved. In this study, a functional nanosystem encapsulated with benzothiazole complexes (FeTB2) and the photosensitizer indocyanine green (ICG) was designed for highly effective antitumor therapy. The surface of the nanocarriers was modified with dihydroartemisinin (DHA)-grafted polyglutamic acid. The induced hyperthermia enables the lipid-polymer shell to depolymerize, releasing FeTB2. The released FeTB2 could kill tumor cells in two different ways by inhibiting DNA replication and catalyzing H2O2 to produce active •OH. Moreover, the conjugated DHA could increase the amount of peroxides in tumor cells and significantly enhance the ROS yield. This work has provided solid evidence that the present nanosystem enables a significant effect on tumor killing through the combined inhibition of DNA replication and ROS-mediated oxidative damage by regulation of the tumor microenvironment, providing a ROS-mediated high-efficiency antitumor strategy.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Benzotiazóis/química , Peróxido de Hidrogênio/química , Ferro/química , Nanopartículas/química , Espécies Reativas de Oxigênio/metabolismo , Células A549 , Animais , Apoptose/efeitos dos fármacos , Artemisininas/química , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Radicais Livres/metabolismo , Humanos , Células MCF-7 , Masculino , Camundongos , Camundongos Endogâmicos BALB C
7.
Drug Dev Ind Pharm ; 45(2): 212-221, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30256663

RESUMO

The acridine derivatives can interact with the double-stranded DNA, which is regarded as the biological target of the anticancer drugs in cancer treatment. We designed and synthesized a new series of 1,3-dimethyl-6-nitroacridine derivatives as potential DNA-targeted anticancer agents. These compounds could partially intercalate into the calf thymus DNA, differing from the parent acridine. The results showed that the substitutions of the acridine ring had great effect on DNA binding affinity. The binding constants determined by UV-vis spectroscopy were found to be 105 M-1 grade. Anticancer activity of these compounds was screened using MTT assay. Most compounds inhibited 50% cancer cell growth at concentration below 30 µM, the results were consistent with the DNA binding ability. Compounds 1 and 6 were found to have more effective cytotoxicity, especially in human breast cancer cell lines. To investigate the action mechanism, we studied cell apoptosis, morphological changes, and cell cycle distribution in MCF-7 and MDA-MB-231 cells. Compounds 1 and 6 caused MCF-7 and MDA-MB-231 cells death due to apoptosis, and induced cell apoptosis in a dose-dependent manner. They also had significant effect on cell cycle progression and arrested cell cycle at G2/M phase. The results demonstrated that compounds 1 and 6 are promising candidates for cancer treatment.


Assuntos
Aminacrina/análogos & derivados , Aminacrina/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , DNA de Neoplasias/efeitos dos fármacos , Animais , Neoplasias da Mama/ultraestrutura , Bovinos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Células MCF-7 , Espectrofotometria Ultravioleta , Relação Estrutura-Atividade
8.
Nanotechnology ; 29(1): 015601, 2018 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-29130888

RESUMO

Polymeric biomaterials that can be smartly disassembled through the cleavage of the covalent bonds in a controllable way upon an environmental stimulus such as pH change, redox, special enzymes, temperature, or ultrasound, as well as light irradiation, but are otherwise stable under normal physiological conditions have attracted great attention in recent decades. The 2-(4-aminophenyl) benzothiazole molecule (CJM-126), as one of the benzothiazole derivatives, has exhibited a synergistic effect with cisplatin (CDDP) and restrains the bioactivities of a series of human breast cancer cell lines. In our study, novel NIR-responsive targeted binary-drug-loaded nanoparticles encapsulating indocyanine green (ICG) dye were prepared as a new co-delivery and combined therapeutic vehicle. The prepared drug-loaded polymeric nanoparticles (TNPs/CDDP-ICG) are stable under normal physiological conditions, while burst drugs release upon NIR laser irradiation in a mild acidic environment. The results further confirmed that the designed co-delivery platform showed higher cytotoxicity than the single free CDDP due to the synergistic treatment of CJM-126 and CDDP in vitro. Taken together, the work might provide a promising approach for effective site-specific antitumor therapy.


Assuntos
Antineoplásicos/administração & dosagem , Benzotiazóis/administração & dosagem , Cisplatino/administração & dosagem , Preparações de Ação Retardada/química , Nanopartículas/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Benzotiazóis/farmacocinética , Benzotiazóis/farmacologia , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Cisplatino/farmacocinética , Cisplatino/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Sinergismo Farmacológico , Feminino , Humanos , Hipertermia Induzida/métodos , Verde de Indocianina/administração & dosagem , Verde de Indocianina/farmacocinética , Verde de Indocianina/farmacologia , Raios Infravermelhos
9.
Nanotechnology ; 29(28): 285302, 2018 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-29671411

RESUMO

A novel core-shell type nanoparticle (CSNP) was designed here to target co-delivery of doxorubicin (DOX) and photosensitizer indocyanine green (ICG) to tumor sites by the aid of NIR induced photothermal conversion effect for the purpose of synergistic chemo-photothermal cancer therapy. The electrostatically self-assembled CSNPs were prepared by amino-functionalized mesoporous silica nanoparticles (MSN-NH2) as the positive inner core and DSPE-PEG2000-COOH and DSPE-PEG2000-FA modified lecithin as the negative outer shell. The obtained CSNPs were nanospheres with a uniform size of 47 nm, which were kept stable at 4 °C in PBS (pH = 7). Research on the release of NIR stimulus (808 nm, 1.54 W cm-2, 6 min) manifested that the release property of the CSNPs was controllable under low pH conditions. In addition, specific concentration (40 µg ml-1) ICG-loaded CSNPs, achieving an appropriate temperature up to 45 °C, indicated a desired photothermal conversion efficiency. For targeting the folate receptor, the folate modified CSNPs enabled us to reach a higher cellular uptake by the mean fluorescence intensity. In vitro cell assay, the prepared CSNPs showed outstanding inhibitory efficiency (2.07% cell viability and 91.8% cell apoptosis) on MCF-7 cells for 24 h when irradiated by an 808 nm laser with a power of 1.54 W cm-2 for 6 min. Our research highlights that the prepared nanoparticles hold potential promise for cancer treatment based on photothermal conversion performance and FA-targeted delivery.


Assuntos
Antineoplásicos/uso terapêutico , Hipertermia Induzida , Raios Infravermelhos , Nanopartículas/química , Neoplasias/terapia , Fototerapia , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Humanos , Lipossomos , Nanopartículas/ultraestrutura , Neoplasias/patologia , Tamanho da Partícula
10.
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
11.
J Environ Pathol Toxicol Oncol ; 42(2): 59-77, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36749090

RESUMO

As an important element in regulating the tumor microenvironment (TME), integrin plays a key role in tumor progression. This study aimed to establish prognostic signatures to predict the overall survival and identify the immune landscape of patients with lung adenocarcinoma based on integrins. The Cancer Genome Atlas-Lung Adenocarcinoma (TCGA-LUAD) and Gene Expression Omnibus datasets were used to obtain information on mRNA levels and clinical factors (GSE72094). The least absolute shrinkage and selection operator (LASSO) model was used to create a prediction model that included six integrin genes. The nomogram, risk score, and time-dependent receiver operating characteristic analysis all revealed that the signatures had a good prognostic value. The gene signatures may be linked to carcinogenesis and TME, according to a gene set enrichment analysis. The immunological and stromal scores were computed using the ESTIMATE algorithm, and the data revealed, the low-risk group had a higher score. We discovered that the B lymphocytes, plasma, CD4+ T, dendritic, and mast cells were much higher in the group with low-risk using the CiberSort. Inflammatory processes and several HLA family genes were upregulated in the low-risk group. The low-risk group with a better prognosis is more sensitive to immune checkpoint inhibitor medication, according to immunophenoscore (IPS) research. We found that the patients in the high-risk group were more susceptible to chemotherapy than other group patients, according to the prophetic algorithm. The gene signatures could accurately predict the prognosis, identify the immune status of patients with lung adenocarcinoma, and provide guidance for therapy.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Microambiente Tumoral , Carcinogênese , Integrinas
12.
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
13.
J Healthc Eng ; 2020: 8714070, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32399167

RESUMO

In the nonmedical sputum monitoring system, a practical solution for phlegm stagnation care of patients was proposed. Through the camera, the video images of patients' laryngeal area were obtained in real time. After processing and analysis on these video frame images, the throat movement area was found out. A three-frame differential method was used to detect the throat moving targets. Anomalies were identified according to the information of moving targets and the proposed algorithm. Warning on the abnormal situation can help nursing personnel to deal with sputum blocking problem more effectively. To monitor the patients' situation in real time, this paper proposed a VDS algorithm, which extracted the speed characteristics of moving objects and combined with the DTW algorithm and SVM algorithm for sequence image classification. Phlegm stagnation symptoms of patients were identified timely for further medical care. In order to evaluate the effectiveness, our method was compared with the DTW, SVM, CTM, and HMM methods. The experimental results showed that this method had a higher recognition rate and was more practical in a nonmedical monitoring system.


Assuntos
Algoritmos , Transtornos de Deglutição/diagnóstico , Escarro , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Gravação em Vídeo
14.
J Mater Chem B ; 8(1): 78-87, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31769461

RESUMO

The rigorous reaction conditions (sufficient H2O2 and a low pH value) of an efficient Fenton reaction limit its further biomedical translation. Therefore, it is urgent to improve the efficacy of the Fenton reaction at the tumor site for efficient ferroptotic therapy. Herein, a hypoxia-responsive-Azo-BSA functionalized biomimetic nanoreactor (Fe(iii)-GA/GOx@ZIF-Azo), encapsulating ultrasmall ferric-gallic acid coordination polymer nanoparticles (Fe(iii)-GA) and glucose oxidase (GOx) into a zeolitic imidazolate framework (ZIF), was constructed for tumor ablation through an intensive Fenton reaction accelerated by not only sustained Fe2+ and H2O2 supply but also low pH and photothermal stimulation. Moreover, Azo achieved charge reversal in a hypoxia microenvironment caused by the sustained oxygen consumption by GOx, which resulted in selective and enhanced tumor accumulation based on the hypoxia-activated positive feedback cellular uptake. This rationally designed biomimetic nanoreactor might lay a foundation for the clinical translation of ferroptotic therapy.


Assuntos
Ferroptose/efeitos dos fármacos , Estruturas Metalorgânicas , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes , Hipóxia Tumoral/efeitos dos fármacos , Animais , Compostos Azo/química , Compostos Férricos/química , Ácido Gálico/química , Glucose Oxidase/química , Humanos , Imidazóis/química , Células MCF-7 , Estruturas Metalorgânicas/farmacologia , Estruturas Metalorgânicas/uso terapêutico , Camundongos , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Microambiente Tumoral/efeitos dos fármacos , Zeolitas/química
15.
J Control Release ; 321: 734-743, 2020 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-32145265

RESUMO

Tumor microenvironment (TME)-responsive nanoformulations that catalyze a cascade of intracellular redox reactions showed promise for tumor treatment with high specificity and efficiency. In this study, we report Cu2+-doped zeolitic imidazolate frameworks-coated polydopamine nanoparticles (PDA@Cu/ZIF-8 NPs) for glutathione-triggered and photothermal-reinforced sequential catalytic therapy against breast cancer. In the TME, the PDA@Cu/ZIF-8 NPs could initially react with antioxidant glutathione (GSH), inducing GSH depletion and Cu+ generation. Whereafter, the generated Cu+ would catalyze local H2O2 to produce highly toxic hydroxyl radicals (·OH) through an efficient Fenton-like reaction even in weakly acidity. Importantly, the PDA could exert excellent photothermal conversion effect to simultaneously accelerate GSH consumption and improve the Fenton-like reaction for further expanding the intracellular oxidative stress, which innovatively achieves a synergistic photothermal-chemodynamic therapy for highly efficient anticancer treatment.


Assuntos
Neoplasias da Mama , Glutationa , Nanopartículas , Microambiente Tumoral , Neoplasias da Mama/terapia , Catálise , Linhagem Celular Tumoral , Glutationa/farmacologia , Humanos , Peróxido de Hidrogênio
16.
ACS Appl Mater Interfaces ; 12(2): 1963-1972, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31873002

RESUMO

Photodynamic therapy (PDT) as a noninvasive therapy mode has attracted considerable attention in the field of oncotherapy. However, the PDT efficacy is restricted either by the tumor hypoxia environment or the inherent properties of photosensitizers (PSs) including bad water solution, photobleaching, and easy aggregation. Herein, we designed and synthesized a new two-dimensional (2D) metal-organic framework, Sm-tetrakis(4-carboxyphenyl)porphyrin (TCPP) nanosheets, by assembling transition metal ions (Sm3+) and PSs (TCPP), on which the catalase (CAT)-mimicking platinum nanozymes were then in situ grown for sufficient oxygen supply during PDT. The prepared Sm-TCPP with nanoplate morphology (∼100 nm in diameter) and ultrathin thickness (<10 nm) showed significantly enhanced 1O2 generation capacity due to the improved physicochemical properties and the enhanced intersystem crossing from heavy Sm nodes. More importantly, the CAT-mimicking Pt nanozyme on the Sm-TCPP nanosheets could effectively convert over-expressed H2O2 in the tumor microenvironment into O2 to relieve tumor hypoxia. Further, the triphenylphosphine (TPP) molecule was introduced to Sm-TCPP-Pt to develop a mitochondrion-targeting and O2 self-supply PDT system. The in vitro and in vivo experimental results based on the MCF-7 breast cancer model revealed that Sm-TCPP-Pt/TPP could relieve tumor hypoxia and the generated reactive oxygen species nearby intracellular mitochondria significantly induced cell apoptosis. This study offers an engineering strategy to integrate 2D PS-based metal-organic frameworks and nanozymes into a nanoplatform to surmount the pitfalls of traditional PDT.


Assuntos
Materiais Biomiméticos/farmacologia , Catalase/metabolismo , Estruturas Metalorgânicas/farmacologia , Mitocôndrias/metabolismo , Nanopartículas/química , Oxigênio/farmacologia , Fotoquimioterapia , Platina/farmacologia , Antineoplásicos/farmacologia , Catálise , Humanos , Luz , Células MCF-7 , Nanopartículas/ultraestrutura , Porfirinas , Espécies Reativas de Oxigênio/metabolismo , Difração de Raios X
17.
Nanoscale ; 12(15): 8139-8146, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32236229

RESUMO

Recent studies have suggested that the anticancer activity of disulfiram (DSF, an FDA-approved alcohol-abuse drug) is Cu-dependent. Low system toxicity and explicit pharmacokinetic characteristics of DSF necessitate safe and effective Cu supplementation in local lesion for further applications. Herein, we presented a new conceptual 'nanosized coordination transport' strategy of Cu(ii) that was realized in porphyrin-based metal-organic frameworks, Sm-TCPP, with strong binding ability to Cu(ii) due to their coordination interactions. Sm-TCPP(Cu) was coated by hyaluronic acid (HA) that termed by Sm-TCPP(Cu)@HA, acting as 'beneficial horse' to target the tumor-localized HA receptor (CD44), thus liberating Cu(ii) ions in cellular overexpressed reductants. The CD44-mediated Cu(ii) accumulation efficiency of Sm-TCPP(Cu)@HA was benchmarked in vitro and vivo against the free TCPP (Cu) via ICP-MS analysis. More importantly, the sensitization effects of Sm-TCPP(Cu)@HA on the anticancer activity of DSF were demonstrated in vivo and in vitro. This study offered a new class of targeted Cu supplements to sensitize DSF for the effective treatment of cancer and established a versatile methodology for constructing a safe and specific delivery of metal ions within living organisms.


Assuntos
Cobre/administração & dosagem , Dissulfiram/administração & dosagem , Sistemas de Liberação de Medicamentos , Receptores de Hialuronatos/metabolismo , Nanoestruturas/administração & dosagem , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Cobre/química , Portadores de Fármacos , Feminino , Humanos , Ácido Hialurônico/química , Ácido Hialurônico/metabolismo , Camundongos , Nanoestruturas/química , Porfirinas/química , Samário/química , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Colloids Surf B Biointerfaces ; 189: 110810, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32014651

RESUMO

In this study, a versatile doxorubicin (DOX)-loaded yolk-shell nano-particles (HMCMD) assembled with manganese dioxide (MnO2) as the core and copper sulfide (HMCuS) as the mesoporous (∼ 6.4 nm) shell, was designed and synthesized. The resulting HMCMD possess excellent photothermal conversion efficiency. The DOX release from the yolk-shell nanoparticles could be promoted by laser irradiation, which increased the chemotherapy of DOX. Meanwhile, Mn2+ could be released from the HMCMD through a redox reaction between MnO2 and abundant glutathione (GSH) in tumor cells. The released Mn2+ could promote the decomposition of the intracellular hydrogen peroxide (H2O2) by Fenton-like reaction to generate the highly toxic hydroxyl radicals (·OH), thus exhibiting the effective chemodynamic therapy (CDT). Additionally, the efficiency of Mn2+-mediated CDT could be effectively enhanced by NIR irradiation. Further modification of polyethylene glycol (PEG) would improve the water solubility of the HMCMD to promote the uptake by MCF-7 cells. Hence, the HMCMD with synergistic effects of chemotherapy and chemodynamic/photothermal therapy would provide an alternative strategy in antitumor research.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Glutationa/antagonistas & inibidores , Nanopartículas/química , Antibióticos Antineoplásicos/síntese química , Antibióticos Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Doxorrubicina/síntese química , Doxorrubicina/química , Liberação Controlada de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Glutationa/metabolismo , Humanos , Raios Infravermelhos , Células MCF-7 , Tamanho da Partícula , Propriedades de Superfície , Células Tumorais Cultivadas
19.
Dalton Trans ; 48(45): 16861-16868, 2019 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-31710076

RESUMO

The efficiency of photosensitizers in tumor photodynamic therapy (PDT) often compromises their poor water solubility, low extinction coefficients, photobleaching, and dissatisfactory reactive oxygen species (ROS) generation efficiency. Herein, a nanoscale 2D metal-organic framework, Sm-H2TCPP nanosheets, was first synthesized by Sm3+-driven coordination with a porphyrin derivative (tetrakis(4-carboxyphenyl)porphyrin (H2TCPP)) for highly effective PDT of breast cancer. The prepared Sm-H2TCPP possessed nanoplate morphology with ultrathin thickness at the sub-10 nm level and an ultrasmall plane size at the sub-100 nm level. Compared with free H2TCPP, the prominent ROS generation capacity of the well-defined Sm-H2TCPP nanosheets is mainly attributed to their improved physicochemical properties and the enhanced intersystem crossing caused by heavy Sm nodes. The significantly improved PDT efficacy of the Sm-H2TCPP nanosheets was further investigated in vitro and in vivo based on the MCF-7 breast cancer model. It is envisaged that the Sm-H2TCPP nanosheets will offer a new avenue for the development of a new class of potential PDT agents.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Estruturas Metalorgânicas/farmacologia , Metaloporfirinas/farmacologia , Nanopartículas/química , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Células MCF-7 , Estruturas Metalorgânicas/síntese química , Estruturas Metalorgânicas/química , Metaloporfirinas/síntese química , Metaloporfirinas/química , Tamanho da Partícula , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Espécies Reativas de Oxigênio/metabolismo , Propriedades de Superfície
20.
Colloids Surf B Biointerfaces ; 176: 230-238, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30623810

RESUMO

Tumor cells experience higher chemotherapy stress under condition of elevated temperature. As a result, developing novel nanoagents that integrates chemotherapy and thermotherapy holds great promise in biomedicine. Herein, utilizing spatially confined galvanic replacement method, we fabricated a yolk-shell Au@mSiO2 nanoframes with Au NPs and mesoporous silica as yolk and shell, respectively, to sever as an excellent drug nanocarrier with effective photothermal conversion efficiency. Taking full advantage of the high temperature response of the Au@mSiO2 nanoframes, the phase change material 1-tetradecanol (TD) was creatively employed as gatekeepers, intelligently controlling the release of loaded agents. Then, the actively targeted Alanine-Alanine-Asparagine, legumain-recognizable oligopeptides was decorated on the surface of the prepared nanoframes. Upon exposure to near-infrared light, the GC-PtAu@mSiO2-TD nanoframes not only exhibited a high localized temperature response, but also triggered the quick release of loaded cargos, and thus improved the chemotherapeutic efficacy. The in vitro cytotoxicity studies indicated the remarkable synergistic effects. Meanwhile, the laser confocal studies and flow cytometry showed the oligopeptides facilitated the intracellular uptake of GC-PtAu@mSiO2-TD nanoframes in MGC-803 cells. Our study highlighted the great potential of the GC-PtAu@mSiO2-TD nanoframes in drug delivery and the combination of chemotherapy and photothermal therapy.


Assuntos
Materiais Revestidos Biocompatíveis/química , Sistemas de Liberação de Medicamentos , Ouro/química , Hipertermia Induzida , Nanopartículas/química , Fototerapia , Dióxido de Silício/química , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cisplatino/farmacologia , Terapia Combinada , Preparações de Ação Retardada/farmacologia , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Humanos , Nanopartículas/ultraestrutura , Nanosferas/química , Porosidade
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