Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 38
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Mater Chem B ; 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34821894

RESUMO

Phototheranostics has attracted great interest in cancer therapy. Small-molecule self-reporting photosensitizers, one kind of idea agent in phototheranostics, enables simultaneous photodynamic therapy (PDT) and feedback of therapeutic efficacy. However, previous such photosensitizers exclusively employed the change of single emission to monitor cell death, which can be disturbed by variations in photosensitizer concentration and the excitation intensity. Herein, we report a unique self-reporting photosensitizer TPA-3PyA+ constructed from a twisted triphenylamine unit (TPA), three benzene ring units and three cyanovinyl-pyridinium units (PyA) for PDT and its real-time monitoring in a dynamic dual-color mode. TPA-3PyA+ possesses a rotatable electron donor-π bridge-electron acceptor framework and exhibits high singlet oxygen quantum yield (124%) and a twisted intramolecular charge transfer (TICT) effect. TPA-3PyA+ not only enables effective staining of cancer cells with dual-color fluorescence due to the TICT effect but also shows excellent PDT performance. The simultaneous change in emission color, intensity and intracellular location of TPA-3PyA+ during cell death allows it to self-report cell death. Moreover, the change of dual-emission color allows distinguishing living and dead cells and effectively avoids interference in previous single-emission self-reporting photosensitizers. This work highlights the great potential of a self-reporting photosensitizer with dual-color emissions for efficient feedback of theranostics.

2.
Front Pharmacol ; 12: 715176, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335277

RESUMO

Abuse of methamphetamine (METH), an illicit psychostimulant, is a growing public health issue. METH abuse during pregnancy is on the rise due to its stimulant, anorectic, and hallucinogenic properties. METH can lead to multiple organ toxicity in adults, including neurotoxicity, cardiovascular toxicity, and hepatotoxicity. It can also cross the placental barrier and have long-lasting effects on the fetus. This review summarizes neurotoxicity, cardiovascular toxicity, hepatotoxicity, toxicity in other organs, and biomonitoring of prenatal METH exposure, as well as the possible emergence of sensitization associated with METH. We proposed the importance of gut microbiota in studying prenatal METH exposure. There is rising evidence of the adverse effects of METH exposure during pregnancy, which are of significant concern.

3.
Front Pharmacol ; 12: 716703, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34381368

RESUMO

Methamphetamine (METH) is a major psychostimulant drug of abuse worldwide, and its neurotoxicity has been studied extensively. In addition to neurotoxicity, METH can also induce hepatotoxicity. The underlying mechanism of intestinal microorganisms in METH-induced hepatotoxicity remains unclear. In this study, mice have received antibiotics intragastrically or PBS once each day for 1 week, followed by METH or saline. The antibiotics attenuated METH-induced hepatotoxicity as evidenced by histopathological observation and biochemical analysis; furthermore, they alleviated METH-induced oxidative stress. The effect of antibiotics on METH-induced hepatotoxicity was investigated using RNA-sequencing (RNA-seq). The RNA-seq results demonstrated that antibiotics could regulate 580 differentially expressed genes (DEGs), of which 319 were upregulated after METH treatment and then downregulated with antibiotic pretreatment and 237 were first downregulated after METH administration and then upregulated after antibiotic pretreatment, in addition to 11 upregulated and 13 downregulated ones simultaneously in METH and antibiotic-pretreated groups. RNA-seq analyses revealed that TLR4 is one of the hub genes. Western blot analysis indicated that antibiotics inhibited the increase of TLR4, MyD88 and Traf6 induced by METH. This research suggests that antibiotics may play an important role in preventing METH-induced liver injury by regulating oxidative stress and TLR4/MyD88/Traf6 axis, though further investigation is required.

4.
Talanta ; 233: 122567, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34215063

RESUMO

Photodynamic therapy (PDT) received great attention in cancer therapy due to the advantages of negligible drug resistance, low side effects, and minimal invasiveness. Development of theranostic nanoprobes with specific imaging-guided PDT is of great significance in the field. Herein we report the fabrication of a novel theranostic nanoprobe porphyrin/G-quadruplex conjugated gold/persistent luminescence nanocomposites for imaging-guided PDT. The developed nanoprobe contains NIR-emitting persistent luminescent nanoparticles (PLNP) as the core for autofluorescence-free bioimaging and Au coating on PLNP for facile subsequent DNA conjugation. The DNA sequence is designed to contain G-rich AS1411 aptamer for recognizing the over-expressed cellular nucleolin of cancer cell and forming a G-quadruplex structure to combine with tetrakis (4-carboxyphenyl) porphyrin (TCPP) to realize PDT. The AS1411 aptamer-contained DNA conjugated Au-coated PLNP is rapidly prepared via a freezing method with high content of DNA and good aqueous stability. Meanwhile, TCPP is easily loaded into the G-quadruplex structure formed from G-rich AS1411 aptamer on the surface of Au/PLNP in presence of K+. The theranostic nanoprobe gives integrated merits of PLNP for autofluorescence-free bioimging, TCPP for PDT and AS1411 aptamer-contained DNA for specific binding to cancer cells. This work provides a new specially designed imaging-guided PDT nanoplatform for theranostics.


Assuntos
Fotoquimioterapia , Porfirinas , Linhagem Celular Tumoral , Ouro , Luminescência , Medicina de Precisão
5.
Talanta ; 232: 122395, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34074391

RESUMO

Mycotoxins contamination in agricultural products poses a serious threat to human and animal health, so rapid and sensitive nanosensors for simultaneous determination of multiple mycotoxins in food samples are highly desirable for food safety monitoring. Herein, we report the fabrication of functional dual-colored persistent luminescence nanoparticles (PLNPs) in conjunction with Fe3O4 magnetic nanoparticles as a nanosensor for the simultaneous biosensing of aflatoxin B1 (AFB1) and zearalenone (ZEN) in food samples. Two types of PLNPs with a single excitation wavelength, Zn2GeO4:Mn2+ and Zn1.25Ga1.5Ge0.25O4:Cr3+,Yb3+,Er3+, are employed as the signal units, and aptamers with high affinity and specificity to the corresponding mycotoxins are used as the recognition units. The nanosensor was fabricated by hybridizing the aptamer modified PLNPs with the complementary DNA modified Fe3O4. The developed nanosensor offers the integrated merits of autofluorescence-free detection of persistent luminescence, the high specificity of aptamer and the high speed of magnetic separation, allowing highly sensitive and selective detection of AFB1 and ZEN in food samples with the limits of detection of 0.29 pg mL-1 for AFB1 and 0.22 pg mL-1 for ZEN and the recoveries of 93.6%-103.2% for AFB1 and 94.7%-105.1% for ZEN. This work also provides a novel universal PLNPs-based optical platform for the simultaneous detection of multiple contaminants in complex samples.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Micotoxinas , Zearalenona , Aflatoxina B1/análise , Animais , Contaminação de Alimentos/análise , Humanos , Limite de Detecção , Luminescência , Micotoxinas/análise , Zearalenona/análise
6.
ACS Appl Mater Interfaces ; 13(24): 27895-27903, 2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34101418

RESUMO

Phototherapy holds great promise in the treatment of bacterial infections, especially the multidrug resistant bacterial infections. However, most therapeutic agents are based on the integration of individual photothermal agents and photosensitizers, always in the activated state, and generally lack bacterial specificity, resulting in uncertain pharmacokinetics and serious nonspecific damage to normal tissues. Herein, we report a pH-responsive nanoplatform with synergistic chemo-phototherapy function for smart fluorescence imaging-guided precision sterilization. pH reversible activated symmetric cyanine was designed and prepared as a bacterial-specific imaging unit and PTT/PDT-in-one agent. Meanwhile, a guanidinium-based covalent organic framework (COF) was employed as a nanocarrier and chemotherapy agent to build the intelligent nanoplatform via electrostatic self-assembly. The self-assembly of the PTT/PDT-in-one agent and the COF greatly improves the stability and blood circulation of the PTT/PDT-in-one agent and provides charge-reversed intelligent targeting ability. The developed smart nanoplatform not only enables bacterial-targeted imaging but also possesses chemo/PTT/PDT synergetic high-efficiency bactericidal effects with little side effects, showing great potential in practical applications.


Assuntos
Antibacterianos/uso terapêutico , Corantes Fluorescentes/uso terapêutico , Estruturas Metalorgânicas/uso terapêutico , Fármacos Fotossensibilizantes/uso terapêutico , Infecções Estafilocócicas/diagnóstico por imagem , Infecções Estafilocócicas/tratamento farmacológico , Animais , Antibacterianos/química , Antibacterianos/efeitos da radiação , Escherichia coli/efeitos dos fármacos , Feminino , Corantes Fluorescentes/química , Corantes Fluorescentes/efeitos da radiação , Gadolínio/química , Gadolínio/efeitos da radiação , Indóis/química , Indóis/efeitos da radiação , Raios Infravermelhos , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/efeitos da radiação , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/efeitos da radiação , Terapia Fototérmica , Medicina de Precisão/métodos , Oxigênio Singlete/metabolismo , Staphylococcus aureus/efeitos dos fármacos
7.
Chem Asian J ; 16(15): 2022-2026, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34096181

RESUMO

A vancomycin (Van) modification strategy on a porphyrinic metal-organic framework (MOF) PCN-224 is presented. The obtained Van-PCN-224 gives the combined advantages of porphyrinic MOF and Van with high photosensitive activity and excellent targeted antibacterial activity against Staphylococcus aureus. The features make Van-PCN-224 promising for antimicrobial therapy.


Assuntos
Antibacterianos/farmacologia , Estruturas Metalorgânicas/farmacologia , Porfirinas/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Vancomicina/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Estruturas Metalorgânicas/síntese química , Estruturas Metalorgânicas/química , Testes de Sensibilidade Microbiana , Conformação Molecular , Tamanho da Partícula , Porfirinas/química , Propriedades de Superfície , Vancomicina/química
8.
Chemistry ; 27(39): 10151-10159, 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-33978976

RESUMO

Porphyrinic metal-organic frameworks (MOFs) are promising photosensitizers due to the lack of self-aggregation of porphyrin in aqueous solution. However, how the topology of porphyrinic MOFs affects the generation of singlet oxygen (1 O2 ) is unclear. Here, the effect of the topology of porphyrinic MOFs on their photodynamic performance is reported. Four porphyrinic zirconium MOFs (MOF-525, MOF-545, PCN-223 and PCN-224 with different topologies: ftw, csq, shp and she, respectively) were selected to study the influence of topology on the photodynamic antibacterial performance. The 1 O2 generation and the photodynamic antibacterial performance followed an decreasing order of MOF-545>MOF-525>PCN-224>PCN-223. The results reveal that the pore size, the distance between porphyrin, and the number of porphyrin per Zr6 O8 cluster in MOFs greatly affected 1 O2 generation. This work provides guidance for designing new MOFs for efficient photodynamic sterilization.


Assuntos
Estruturas Metalorgânicas , Porfirinas , Fármacos Fotossensibilizantes , Esterilização , Zircônio
9.
Anal Chem ; 93(19): 7348-7354, 2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-33966391

RESUMO

Persistent luminescence nanoparticles (PLNPs) hold great promise for bioimaging owing to no demand for in situ excitation and negligible tissue autofluorescence interference. Nevertheless, huge challenges remain in the further development of single-emissive PLNPs due to the great variation of luminescence with time after excitation ceases. Herein, we report the controllable fabrication of dual-emissive monodispersed PLNPs (ZnGa2O4:Cr) by a surfactant-assisted hydrothermal method in combination with postcalcination for bioimaging. The prepared PLNPs emit luminescence at 508 and 714 nm with a constant luminescence ratio (I508/I714) for more than 1 h after UV excitation stops. Moreover, the prepared PLNPs give a constant I508/I714 ratio signal after repeated excitation by a LED lamp, allowing luminescence ratio imaging to ensure the long-term accuracy for in vivo imaging. In vivo ratio imaging demonstrates the potential of the prepared PLNPs for precision bioimaging. In addition, the prepared PLNPs have been applied to fabricate a theranostic nanoprobe with intelligent tumor-targeted imaging and chemo-photothermal synergistic therapy to further reveal their unique advantage for imaging guided therapy. We believe that the dual-emissive PLNPs will provide a promising nanoplatform for bioimaging and biomedical applications.


Assuntos
Nanopartículas , Neoplasias , Diagnóstico por Imagem , Humanos , Luminescência
10.
Front Pharmacol ; 12: 641917, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33679421

RESUMO

Misuse of the psychostimulant methamphetamine (METH) could induce serious hepatotoxicity. Our previous study revealed the effects of luteolin on alleviating METH-induced hepatotoxicity, however, the detailed mechanisms have not been elucidated. In this study, rats were orally pretreated with 100 mg/kg luteolin or sodium dodecyl sulfate water, and then METH (15 mg/kg, intraperitoneal [i.p.]) or saline was administered. Histopathological and biochemical analyses were used to determine the alleviative effects of luteolin. Based on the RNA-sequencing data, METH induced 1859 differentially expressed genes (DEGs) in comparison with the control group, which were enriched into 11 signaling pathways. Among these DEGs, 497 DEGs could be regulated through luteolin treatment and enriched into 16 pathways. The p53 signaling pathway was enriched in both METH administered and luteolin pretreated rats. Meanwhile, luteolin significantly suppressed METH-induced elevation of p53, caspase9, caspase3, cleaved caspase3, the ratio of Bax/Beclin-2, as well as autophagy-related Beclin-1, Atg5, and LC3-II. Luteolin also relieved METH-induced hepatotoxicity by decreasing inflammation factors, including TNF-α, IL-1ß, and IL-18. Moreover, the levels of PI3K, p-Akt, and the normalized ratio of p-Akt/Akt declined after METH administration, whereas luteolin pretreatment failed to reverse these effects. Our results suggest that luteolin alleviates METH-induced hepatic apoptosis, autophagy, and inflammation through repressing the p53 pathway. It further illustrates the protective mechanisms of luteolin on METH-induced hepatotoxicity and provides a research basis for clinical treatment.

11.
Talanta ; 225: 122046, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33592768

RESUMO

Near-infrared (NIR) aggregation-induced emission (AIE) of previous organic photosensitizers is usually weak because of the competition between twisted intramolecular charge transfer (TICT) effect and AIE. Herein, we report a rational molecular design strategy to boost NIR AIE of photosensitizers and still to keep strong 1O2 production capacity via rotor effect. To this end, one new triphenylamine (TPA)-based AIE photosensitizer, TPAM-1, is designed to give strong ability to generate 1O2 but weak NIR fluorescence in the aggregate state due to the strong TICT effect. Another new TPA-based AIE photosensitizer, TPAM-2, is designed by introducing three p-methoxyphenyl units as rotors into the structure of TPAM-1 to modulate the competition between AIE and TICT. TPAM-1 and TPAM-2 exhibit stronger ability to generate 1O2 in the aggregate state than the commercial photosensitizer, Ce6. Furthermore, TPAM-2 gives much brighter NIR luminescence (25-times higher quantum yield) than TPAM-1 in the aggregate state due to the rotor effect. TPAM-2 with strong NIR AIE and 1O2 production capability was encapsulated by DSPE-PEG2000 to give good biocompatibility. The DSPE-PEG2000-encapsulated TPAM-2 nanoparticles show good cell imaging performance and remarkable photosensitive activity for killing HeLa cells. This work provides a new way for designing ideal photosensitizers for AIE imaging-guided photodynamic therapy.


Assuntos
Neoplasias , Fotoquimioterapia , Diagnóstico por Imagem , Fluorescência , Células HeLa , Humanos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/farmacologia
12.
Anal Chem ; 93(4): 2589-2595, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33410662

RESUMO

Selective and sensitive determination of trace kanamycin in complex food samples is of great importance for food safety because of its high toxicity. Here, we report a sensitive and autofluorescence-free persistent luminescence (PL) aptasensor for selective, sensitive, and autofluorescence-free determination of kanamycin in food samples. The aptamer for kanamycin was first conjugated onto the surface of magnetic nanoparticles Fe3O4 to serve as the recognition unit as well as the separation element, while the PL nanoparticles ZnGa2O4:Cr (PLNPs) were functionalized with the aptamer complementary DNA (cDNA) as the PL signal. The PL aptasensor consisted of the aptamer-conjugated MNPs (MNPs-apt) and cDNA-functionalized PLNPs (PLNPs-cDNA) and combined the merits of the long-lasting luminescence of PLNPs, the magnetic separation ability of MNPs as well as the selectivity of the aptamer, offering a promising approach for autofluorescence-free determination of kanamycin in food samples. The proposed aptasensor showed excellent linearity in the range from 1 pg mL-1 to 5 ng mL-1 with a limit of detection of 0.32 pg mL-1. The precision for 11 replicate determinations of 100 pg mL-1 kanamycin was 3.1% (relative standard deviation). The developed aptasensor was applied for the determination of kanamycin in milk and honey samples with the recoveries of 95.4-106.3%. The proposed aptasensor is easily extendable to other analytes by simply replacing the aptamer, showing great potential as a universal aptasensor platform for selective, sensitive, and autofluorescence-free detection of hazardous analytes in food samples.


Assuntos
Análise de Alimentos/métodos , Contaminação de Alimentos/análise , Canamicina/química , Medições Luminescentes/métodos , Animais , Técnicas Biossensoriais , Compostos Ferrosos , Mel/análise , Nanopartículas Metálicas , Leite/química , Pós/química
13.
J Cell Physiol ; 236(8): 5453-5465, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33400276

RESUMO

RNF2 (also known as ding, Ring1B or Ring2) is a member of the Ring finger protein family, which functions as E3 ubiquitin ligase for monoubiquitination of histone H2A at lysine 119 (H2AK119ub). RNF2 gene is located at the 1q25.3 site of human chromosome and the coding region is composed of 9 exons, encoding 336 amino acids in total. Many studies have demonstrated that overexpressed RNF2 was involved in the pathological progression of multiple cancers and has an impact on their clinical features. For instance, the upregulated expression level of RNF2 is positively correlated with the occurrence and progression of hepatocellular carcinoma, melanoma, prostate cancer, breast cancer, pancreatic cancer, gastric cancer, and bladder urothelial carcinoma, as well as with the radioresistance of lung cancer and chemoresistance of ovarian cancer. This review provides an up-to-date perspective on the relationship between RNF2 and several cancers and highlights recent studies on RNF2 regulation. In particular, the relevant cellular signaling pathways and potential clinical value of RNF2 in cancers are also discussed, suggesting its potential as an epigenetic biomarker and therapeutic target for these cancers.


Assuntos
Carcinoma de Células de Transição/genética , Regulação Neoplásica da Expressão Gênica/genética , Complexo Repressor Polycomb 1/metabolismo , Neoplasias da Bexiga Urinária/genética , Carcinoma de Células de Transição/metabolismo , Carcinoma de Células de Transição/patologia , Histonas/metabolismo , Humanos , Ubiquitinação , Neoplasias da Bexiga Urinária/metabolismo
14.
Angew Chem Int Ed Engl ; 60(5): 2398-2405, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33073905

RESUMO

Persistent luminescent nanoparticles (PLNPs) with intrinsic stimuli-responsive properties are desirable because of no autofluorescence background and natural responsive luminescence. However, the stimuli-responsive features of pure PLNPs have been unexplored. Here we show a facile one-pot hydrothermal synthesis of green-emitting Zn2 GeO4 :Mn2+ ,Pr3+ nanoparticles (ZGMP) with regular shape, uniform size and good afterglow luminescent performance. We also report the pH stimuli-responsive luminescent behavior of ZGMP and its possible mechanism. Taking the intriguing feature of pH responsive persistent luminescence, we explore ZGMP as autofluorescence-free probes to achieve stimuli-activated signal switch for biosensing by integrating enzyme catalysis reaction mediated pH modulation. The pH-responsive persistent luminescence also makes ZGMP promising for high-level information encryption.


Assuntos
Nanopartículas/química , Técnicas Biossensoriais , Humanos , Luminescência
15.
Food Chem Toxicol ; 148: 111946, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33359793

RESUMO

Methamphetamine (METH) is an addictive and illegal psychostimulant drug that can cause multiple organ dysfunction, especially in the central nervous system (CNS). Gut microbiota have been implicated in development of various CNS-related diseases, via the gut-brain axis (GBA). However, effect of METH in the alteration of gut microbiota and fecal metabolites is unclear, whereas the relationship with METH-induced neurotoxicity remains unknown. In the current study, we investigated effect of METH on neurotoxicity in striatum and colonic damage by exposing BALB/c mice to an escalating dose-multiple binge regimen, and then analyzed protein expression using Western blot analysis. We further detected and sequenced the 16 S rRNA gene in fecal samples, and performed ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS)-based metabolomics to analyze gut microbes and fecal metabolites. Exposure to METH significantly downregulated tyrosine hydroxylase (TH) proteins, but upregulated MAOA, Beclin1, Atg5, and LC3-Ⅱ. METH up-regulated inflammation-related factors, such as caspase1, TNF-α and IL-18, by activating the toll-like receptors 4 (TLR4)/myeloid differentiation factor 88 (Myd88)/nuclear factor κB (NF-κB) pathway and reduced occludin protein expression. In addition, METH exposure changed α and ß diversities of gut microbiota. Specifically, METH exposure elevated relative abundances of pathogenic bacteria, but reduced those of probiotics. Metabolomics, combined with enrichment analyses revealed that METH exposure altered fecal metabolites. Our findings suggest that METH exposure induced autophagy in the CNS, elevated intestinal autophagy flora, leading to accumulation of fecal metabolites in the autophagy pathway, and causing enteritis. Moreover, METH promoted intestinal inflammation by increasing the relative abundance of the pathogenic bacteria in the intestinal tract, and reduced intestinal TJ protein expression.


Assuntos
Estimulantes do Sistema Nervoso Central/toxicidade , Fezes/química , Microbioma Gastrointestinal/efeitos dos fármacos , Metanfetamina/toxicidade , Síndromes Neurotóxicas/etiologia , Animais , Autofagia/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Enterite/induzido quimicamente , Enterite/metabolismo , Masculino , Metabolômica , Camundongos Endogâmicos BALB C , Monoaminoxidase/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Subunidade p50 de NF-kappa B/metabolismo , Síndromes Neurotóxicas/metabolismo , Ocludina/metabolismo , Receptor 4 Toll-Like/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismo , Regulação para Cima/efeitos dos fármacos
16.
Talanta ; 219: 121209, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32887113

RESUMO

Theranostic nano-drug delivery systems are promising candidates for early diagnosis and treatment of tumors. However, it is a great challenge to achieve accurate intracellular delivery and stimuli-responsive drug release with the enhanced anti-tumor effects and reduced side effects. Herein we report the fabrication of polyamide-amine (PAMAM) dendrimer grafted persistent luminescence nanoparticles (PLNPs) via in situ growth of PAMAM on the surface of PLNPs and its application in targeted bioimaging and drug delivery. The developed PLNPs-PAMAM possesses strong renewable near-infrared persistent luminescence for imaging and gives abundant terminal groups for further functionalization. Aptamer AS1411 coupled to the PLNPs-PAMAM surface can specifically bind to the over-expressed nucleolin on the membrane of tumor cells and improve the intracellular accumulation of the nanoparticles. Doxorubicin (DOX) is loaded on PLNPs-PAMAM by a pH-sensitive hydrazine, can be specifically released in the intracellular acid environment, leading to apoptosis of HeLa tumor cells and inhibition of tumor growth. The as-prepared smart drug delivery nanoplatform with persistent luminescence, PLNPs-PAMAM-AS1411/DOX, shows a good application prospect for precise cancer theranostics.


Assuntos
Dendrímeros , Nanopartículas , Neoplasias , Preparações Farmacêuticas , Doxorrubicina/uso terapêutico , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Humanos , Luminescência , Neoplasias/tratamento farmacológico
17.
ACS Appl Mater Interfaces ; 12(41): 45850-45858, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-32975404

RESUMO

Photodynamic sterilization is the most promising method to combat bacterial infection, especially multidrug-resistant bacterial infection. However, the absorption of conventional photosensitizers is mostly located in the UV-vis region, leading to limited penetration depth and poor therapeutic efficacy for deep-tissue bacterial infection. Besides, most of the photosensitizers are always in the activated state and lack bacteria-targeting ability, which inevitably causes severe nonspecific damage to normal tissues. Here, we show the design of a pH reversibly switchable near-infrared photosensitizer-based nanocapsule for precision bacteria-targeting fluorescence imaging-guided photodynamic sterilization. pH reversibly activatable asymmetric cyanine was synthesized as a bacteria-specific imaging unit and smart photosensitizer to realize precision imaging-guided targeting sterilization without side effects. An allicin mimic was introduced into the smart photosensitizer as the auxiliary bactericidal group to further enhance antibacterial efficiency. Meanwhile, amphipathic functionalized polyethylene glycol was employed to fabricate the nanocapsule by self-assembly to endow the charge-reversed intelligent targeting ability and prolong blood circulation. The developed switchable nanocapsule not only enables precision bacterial infection-targeted imaging without background fluorescence interference but also gives an efficient bactericidal effect with excellent specificity and negligible side effects, holding great potential for practical application.


Assuntos
Antibacterianos/farmacologia , Nanocápsulas/química , Imagem Óptica , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Animais , Antibacterianos/química , Sobrevivência Celular/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Raios Infravermelhos , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Células NIH 3T3 , Fármacos Fotossensibilizantes/química , Staphylococcus aureus/efeitos dos fármacos
18.
PeerJ ; 8: e9720, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32864221

RESUMO

Polychlorinated biphenyls (PCBs), particularly low chlorinated congeners in our environment, can induce human hepatotoxicity. However, the mechanisms by which PCBs cause hepatotoxicity remain elusive. Moreover, there are no effective treatments for this condition. In this study, 40 µM PCB52 was administered to rat (Brl-3A) and human hepatocytes (L-02) for 48 h following the N-acetylcysteine (NAC)/saline pretreatment. A significant decrease in cell viability was observed in PCB52-treated cells relative to the control. Besides, PCB52 significantly increased reactive oxygen species (ROS) levels and malondialdehyde (MDA) contents, suggesting induction of oxidative stress. The expression of Traf6, MyD88, and Tnf in Brl-3A cells and that of MYD88, TNF, and IL1B in L-02 cells were significantly upregulated by PCB52. Consistently, overexpression of TLR4, MyD88, Traf6, and NF-κB p65 proteins was observed in PCB52-treated cells, indicating activation of inflammatory responses. Nevertheless, no changes in kelch-like ECH-associated protein 1 (keap1), nuclear factor-erythroid 2-related factor (nrf2), and heme oxygenase-1 proteins were observed in PCB52-treated cells, indicating non-activation of the keap1/nrf2 pathway. Pretreatment with NAC significantly ameliorated PCB52 effects on cell viability, ROS levels, MDA contents and expression of inflammatory elements at both RNA and protein levels. However, no changes in keap1, nrf2 and HO-1 protein levels were detected following NAC pretreatment. Taken together, with non-activated keap1/nrf2 pathway, PCB52-induced oxidative stress and inflammatory responses could be responsible for its hepatotoxicity. These effects were effectively attenuated by NAC pretreatment, which scavenges ROS and dampens inflammatory responses. This study might provide novel strategies for the treatment of the PCBs-associated hepatotoxic effects.

19.
J Mater Chem B ; 8(35): 8071-8083, 2020 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-32785386

RESUMO

Efficient drug nanocarriers with high drug loading capacity and luminescent ability are in high demand for biomedical applications. Here we show a facile and bio-friendly synthesis of macrophage membrane coated persistent luminescence nanoparticle (PLNP)@metal-organic framework (MOF)-derived mesoporous carbon (MC) core-shell nanocomposites (PLMCs) for autofluorescence-free imaging-guided chemotherapy. MOF UiO-66 is used as both the precursor and the template, and is controllably coated on the surface of the PLNP to form a PLNP@UiO-66 core-shell composite. Subsequent calcination enables the transformation of PLNP@UiO-66 to PLMC due to the pyrolysis of the UiO-66 shell. PLMC with a small particle size of 70 nm, a tunable large pore size from ∼4.8 to ∼16.2 nm in the shell and near-infrared persistent luminescence in the core was prepared by controlling the calcination conditions. The prepared PLMC showed an enhanced drug loading capacity for three model drugs (doxycycline hydrochloride, acetylsalicylic acid, and paclitaxel) compared with PLNP@UiO-66. Further coating of the macrophage membrane on the surface of PLMC results in MPLMC with enhanced cloaking ability for evading the mononuclear phagocyte system. The drug-loaded MPLMC is promising for autofluorescence-free persistent luminescence imaging-guided drug delivery and tumor therapy.


Assuntos
Carbono/química , Membrana Celular/metabolismo , Macrófagos/citologia , Estruturas Metalorgânicas/química , Nanocompostos/química , Nanopartículas/química , Imagem Óptica , Linhagem Celular Tumoral , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Humanos , Tamanho da Partícula , Porosidade
20.
Talanta ; 218: 121101, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32797868

RESUMO

Serious ochratoxin A (OTA) contamination necessitates the development of rapid, sensitive and selective analytical methods for its determination in food safety. Herein, we report a persistent luminescence resonance energy transfer (LRET) based aptasensor for the autofluorescence-free detection of OTA. OTA aptamer functionalized persistent luminescence nanorod (PLNR) Zn2GeO4:Mn2+ and the aptamer complementary DNA modified gold nanoparticle (AuNP) were used as the donor and the acceptor, respectively. The developed LRET aptasensor integrated the advantages of the long-lasting persistent luminescence of PLNR, the high selectivity of aptamer and the low probe background of LRET sensors, allowing autofluorescence-free detection of OTA in biological samples with high sensitivity and selectivity. The developed LRET aptasensor gave an excellent linearity in the range of 0.01-10 ng mL-1, the detection limit of 3 pg mL-1 and the precision of 2.7% (RSD, n = 11) at 1 ng mL-1 level. The applicability of the developed aptasensor was demonstrated by analyzing beer samples for OTA with the recoveries of 92.3%-104%.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Nanopartículas Metálicas , Micotoxinas , Nanotubos , Ocratoxinas , Ouro , Limite de Detecção , Luminescência , Ocratoxinas/análise
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...