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1.
Cytometry A ; 97(1): 31-38, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31403260

RESUMO

Pathological diagnosis plays an important role in the diagnosis and treatment of hepatocellular carcinoma (HCC). The traditional method of pathological diagnosis of most cancers requires freezing, slicing, hematoxylin and eosin staining, and manual analysis, limiting the speed of the diagnosis process. In this study, we designed a one-dimensional convolutional neural network to classify the hyperspectral data of HCC sample slices acquired by our hyperspectral imaging system. A weighted loss function was employed to promote the performance of the model. The proposed method allows us to accelerate the diagnosis process of identifying tumor tissues. Our deep learning model achieved good performance on our data set with sensitivity, specificity, and area under receiver operating characteristic curve of 0.871, 0.888, and 0.950, respectively. Meanwhile, our deep learning model outperformed the other machine learning methods assessed on our data set. The proposed method is a potential tool for the label-free and real-time pathologic diagnosis. © 2019 International Society for Advancement of Cytometry.

2.
Adv Healthc Mater ; 9(1): e1900996, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31746153

RESUMO

Photodynamic therapy (PDT) usually aggravates tumor hypoxia, which promotes the survival and metastasis of residue cancer cells; furthermore, although PDT-induced immunogenic death of cancer cells can induce host antitumor responses, such responses are generally weak and not enough to eliminate the residue cancer cells. Here, metal-organic framework (MOF)-based nanoparticles to combine PDT, antihypoxic signaling, and CpG adjuvant as an in situ tumor vaccine to boost host anticancer responses after PDT are designed. The MOF-based nanoparticles are self-assembled from H2 TCPP and zirconium ions with hypoxia inducible factor (HIF) signaling inhibitor (ACF) and immunologic adjuvant (CpG) loading, and hyaluronic acid (HA) coating on the surface. The final nanoparticles (PCN-ACF-CpG@HA) can specifically target cancer cells overexpressing CD44 receptor though HA; the aggravated hypoxic survival signaling after PDT can be blocked by ACF to inhibit the HIF-1α induced survival and metastasis. With the help of CpG adjuvant, the tumor associated antigens generated from PDT-based cancer cell destruction can initiate strong antitumor immune responses to eliminate residue cancer cells. Taken together, a novel in situ immunostimulatory strategy is designed to synergistically enhance therapeutic effects of PDT by activating host antitumor immune-responses both in vitro and in vivo, which may have great potential for clinical translation in future.

3.
Gene ; : 144265, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31805318

RESUMO

To explore its roles in adipogenesis, the levels of genomic 5mC methylation were examined across the adipocyte differentiation of 3 T3-L1 cells. This led to the identification of an up-regulating 5mC profile during the process. To further explore the regulation, gene expression assay was performed with a set of 5mC metabolic enzymes. Among them, TET2 was found to be the most regulated 5mC demethylase, in addition to a well-investigated 5mC methylase DNMT1. In the process, the expression of Tet2 increased for over 16-fold, suggesting its implications in the differentiation. Therefore, loss-of-function and gain-of-function assays were performed with Tet2. It was found that in relative to the differentiation of wild-type cells, knockdown of Tet2 expression led to greatly enhanced differentiation process, while over-expression of the gene resulted in repressed differentiation. Pathway study found that during the differentiation, TET2 demethylates Adrb3 promoter to up-regulate its expression. This led to enhanced lipolysis and decreased lipid production. To the upstream pathway, vitamin C treatment was found to enhance the activity of TETs, decrease 5mC levels and repress lipid production. Taken together, TET2 was characterized as an anti-adipogenic demethylase in adipocyte differentiation of 3 T3-L1 cells.

4.
Am J Cancer Res ; 9(10): 2064-2078, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31720075

RESUMO

The activating receptor natural killer group 2, member D (NKG2D) is involved in both innate and adaptive immunities, and functions as a "master switch" in determining the activation status of natural killer (NK) cells. NKG2D binds to a diverse family of ligand molecules, which are only expressed at low levels in normal cells but can be upregulated by a cellular stress response. The NKG2D-NKG2D ligand (NKG2DL) pathway has been considered to be promising target for immunotherapy because of the selective expression of "stress-induced ligands" on tumor cells and the strong NK cell activating potency of NKG2D. Diverse strategies that are aimed at targeting the NKG2D pathway for cancer therapy are based on a thorough understanding of this mechanism, as well as that of NKG2D-mediated cancer immunity. In this review, we summarize the major findings regarding the antitumor immune response mediated by the NKG2D receptor and its ligands, and discuss the potential clinical applications of targeting the NKG2D/NKG2DL pathway for immunotherapy in cancer patients.

5.
ACS Appl Mater Interfaces ; 11(45): 41829-41841, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31617343

RESUMO

Photodynamic therapy (PDT) is an encouraging alternative therapy for melanoma treatment and Ce6-mediated PDT has shown some exciting results in clinical trials. However, PDT in melanoma treatment is still hampered by some melanoma's protective mechanisms like antiapoptosis mechanisms and treatment escape pathways. Combined therapy and enhancing immune stimulation were proposed as effective strategies to overcome this resistance. In this paper, a Chlorin-based photoactivable Galectin-3-inhibitor nanoliposome (PGIL) was designed for enhanced Melanoma PDT and immune activation of Natural Killer (NK) cells. PGIL were synthesized by encapsulating the photosensitizer chlorin e6 and low molecular citrus pectin in the nanoliposome to realize NIR-triggered PDT and low molecular citrus pectin (LCP) release into the cytoplasm. The intracellular release of LCP inhibits the activity of galectin-3, which increases the apoptosis, inhibits the invade ability, and enhances the recognition ability of Natural Killer (NK) cells to tumor cells in melanoma cells after PDT. These effects of PGIL were tested in cells and nude mice, and the mechanisms during the in vivo treatment were preliminarily studied. The results showed that PGIL can be an effective prodrug for melanoma therapy.

6.
Mikrochim Acta ; 186(8): 568, 2019 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-31338601

RESUMO

A bioinspired fluorometric method has been developed for the detection of glutathione (GSH) in biological fluids. It is based on the use of near-infrared fluorescent semiconducting polymer dots (P-dots) and of the dopamine (DA)-melanin nanosystem. The P-dots were prepared from poly(styrene-co-maleic anhydride), the semiconducting polymer poly[(9,9'-dioctyl-2,7-divinylenefluorenylene)-alt-2-methoxy-5-(2-ethyl-hexyloxy)-1,4-phenylene] and the fluorescent dye tetraphenylporphyrin. They have excitation/emission maxima at 458/656 nm, and this enables measurement to be performed with low autofluorescence and scattering background. DA can self-polymerize on the surface of the P-dots to yield a poly-DA coating. This coating, at weak alkaline pH values, causes the quenching of the fluorescence of the P-dots. However, the polymerization of DA is inhibited by GSH. Hence, quenching of fluorescence is prevented. This effect was used to design a fluorometric assay for GSH that has good selectivity and sensitivity. Under optimal conditions, the method has a linear response in the 0.2 to 20 µM GSH concentration range and a 60 nM detection limit. It was successfully applied to the determination of GSH in HepG2 cells and in spiked human serum. Graphical abstract Schematic representation of using a NIR fluorescent P-dots and dopamine (DA)-melanin nanohybrid as a probe for glutathione (GSH) detection. The P-dots were prepared from poly(styrene-co-maleic anhydride) (PSMA), the semiconducting polymer poly[(9,9'-dioctyl-2,7-divinylenefluorenylene)-alt-2-methoxy-5-(2-ethyl-hexyloxy)-1,4-phenylene] (PEPV) and the fluorescent dye tetraphenylporphyrin (TPP).The GSH can inhibit the dopamine self-polymerization and prevented the formation of PDA and fluorescence quenching of P-dots.

7.
Mikrochim Acta ; 186(8): 491, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31267269

RESUMO

A multifunctional nanoprobe is described for dual sensing of acidic pH values and glutathione (GSH) by combining the pH-responsive fluorescent probe 3-acetyl-7-hydroxy-2H-chromen-2-one (AHC) and MnO2 nanosheets. The fluorescence of the MnO2/AHC composite is weak due to an inner filter effect. If, however, the MnO2 nanosheets are reductively decomposed by GSH, the blue fluorescence of the pH probe AHC (with excitation/emission maximum at 417/456 nm) will be restored. The MnO2 nanosheets also are decomposed by acidic pH values, and the fluorescence of AHC is decreased. According to absorbance and fluorescence signal changes, the pH and GSH induced responses can be easily distinguished. Thus, the nanoprobe can be used for logical analysis of acidic pH values and GSH. The nanoprobe works in the pH range from 4 to 7, and GSH can be determined in the concentration range from 0.5 to 200 µM. Graphical abstract Schematic presentation of a multifunctional nanoprobe for dual sensing of acidic pH values and glutathione by combining a pH-responsive fluorescent probe and MnO2 nanosheets. According to absorbance and fluorescence signal changes, the nanoprobe can be used for logical analysis.

8.
Opt Express ; 27(4): 4672-4693, 2019 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-30876080

RESUMO

We study the energy spectrum of laser-induced conduction band (CB) electrons in water by multi-rate equations (MRE) with different impact ionization schemes. Rethfeld's MRE model [Phys. Rev. Lett.92, 187401(2004)Phys. Rev.B 79, 155424(2009)], but the corresponding rate equations are computationally very expensive. We introduce a simplified splitting scheme and corresponding rate equations that still agree with energy conservation but enable the derivation of an asymptotic SRE. This approach is well suited for the calculation of energy spectra at long pulse durations and high irradiance, and for combination with spatiotemporal beam propagation/plasma formation models. Using the energy-conserving MREs, we present the time-evolution of CB electron density and energy spectrum during femtosecond breakdown as well as the irradiance dependence of free-electron density, energy spectrum, volumetric energy density, and plasma temperature. These data are relevant for understanding photodamage pathways in nonlinear microscopy, free-electron-mediated modifications of biomolecules in laser surgery, and laser processing of transparent dielectrics in general.

9.
Cancer Genet ; 231-232: 1-13, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30803551

RESUMO

T-cell acute lymphoblastic leukemia (T-ALL) is not as frequently reported as the B-cell counterpart (B-ALL), only occurring in about 15% of pediatric cases with a typically heterogeneous etiology. Approximately 8% of childhood T-ALL cases have rearrangements involving the ABL1 tyrosine kinase gene at 9q34.12; although a t(9;22), resulting in a fusion of ABL1 with the BCR gene at 22q11.23 is a common occurrence in B-ALL, it is not a typical finding in T-ALL. A subset of 10 of 40 documented cases of T-ALL analyzed over a 5-year period is presented, each having gene rearrangements within band 9q34 that resulted in fusions other than BCR/ABL1. These cases included fusions involving ABL1, SET (9q34.11), NUP214 (9q34.13), SPTAN1 (9p34.11), and TNRC6B (22q13.1). Among the 10 cases are: six SET/NUP214 fusions, two ABL1/NUP214 fusions (one of which was associated with episomal amplification) and novel SPTAN1/ABL1 and TNRC6B/ABL1 fusions. The evaluations of these clones were each significantly aided by FISH analysis, which directed subsequent microarray and anchored multiplex PCR testing for fusion confirmations.


Assuntos
Cromossomos Humanos Par 9/genética , Proteínas de Fusão Oncogênica/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Adolescente , Criança , Pré-Escolar , Humanos
10.
J Biomed Opt ; 23(12): 1-12, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30552757

RESUMO

Photoacoustic responses induced by laser-excited photothermal bubbles (PTBs) in colloidal gold solutions are relevant to the theranostics quality in biomedical applications. Confined to the complexity of nonstationary, multiscale events, and multiphysical parameters of PTBs, systematic studies of the photoacoustic effects remain obscure. Photoacoustic effects mediated by PTB dynamics and a physical mechanism are studied based on a proof-of-principle multimodal platform integrating side-scattering imaging, time-resolved optical response, and acoustic detection. Results show excitation energy, nanoparticle (NP) size, and NP concentration have strong influence on photoacoustic responses. Under the characteristic enhancement regime, the photoacoustic signal amplitude increases linearly with excitation energy and increases quadratically with the NP diameter. As for the effects of the NP concentration (characterized by absorption coefficient), a higher photoacoustic signal amplitude is generally induced by a dense NP distribution. However, with an increase in the NP size, the shielding effect of NP swarm prevents the increase of photoacoustic responses. This study presents experimental evidence of some key physical phenomena governing the PTB-induced photoacoustic signal generation in gold NP suspensions, which may help enrich theranostic approaches in clinical applications by rationalizing operation parameters.


Assuntos
Nanopartículas/química , Técnicas Fotoacústicas/métodos , Nanomedicina Teranóstica/métodos , Desenho de Equipamento , Coloide de Ouro/química , Modelos Químicos , Técnicas Fotoacústicas/instrumentação , Volatilização
11.
Opt Express ; 26(22): 28560-28575, 2018 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-30470031

RESUMO

Multiple breakdowns in liquids still remains obscure for its complex, non-equilibrium and transient dynamic process. We introduced three methods, namely, plasma imaging, light-scattering technique, and acoustic detection, to measure the multiple breakdown in water induced by focused nanosecond laser pulses simultaneously. Our results showed that linear dependence existed among the cavitation-bubble lifetime, the far-field peak pressure of the initial shock wave, and the corresponding plasma volume. Such a relationship can be used to evaluate the ideal size and energy of each bubble during multiple breakdown. The major bubble lifetime was hardly affected by the inevitable coalescence of cavitation bubbles, thereby confirming the availability of light-scattering technique on the estimation of bubble size during multiple breakdown. Whereas, the strength of collapse-shock-wave and the subsequent rebound of bubbles was strongly influenced, i.e., the occurrence of multiple breakdown suppressed the cavitation-bubble energy being converted into collapse-shock-wave energy but enhanced conversion into rebound-bubble energy. This study is a valuable contribution to research on the rapid mixing of microfluidics, damage control of microsurgery, and photoacoustic applications.

12.
Analyst ; 144(1): 265-273, 2018 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-30398232

RESUMO

A conductometric immunoassay protocol was designed for the sensitive detection of a liver cancer biomarker, alpha-fetoprotein (AFP), in biological fluids by using enzyme-conjugated nanometer-sized enzyme-doped silica beads. Initially, urease molecules were doped into nanosilica particles by using the reverse micelle method. Thereafter, arginase-labeled anti-AFP antibodies were covalently conjugated onto the surface of the synthesized nanoparticles. The immunoreaction was carried out in a monoclonal anti-AFP capture antibody-coated microplate with a sandwich-type assay format by using bienzyme-functionalized silica nanobeads as the recognition elements. Upon l-arginine introduction, the substrate was cleaved into urea and l-ornithine on the basis of the arginase enzymatic reaction, and the as-produced urea was then decomposed into ammonia (NH4+) and bicarbonate (HCO3-) ions by the doped urease, thus causing the variation in the local conductivity of the detection solution on an interdigitated conductometric transducer. Under optimal conditions, the developed immunosensing system exhibited good conductometric responses toward target AFP within a dynamic linear range of 0.01-100 ng mL-1 at a relatively low detection limit of 4.8 pg mL-1 based on the 3sB criterion. Importantly, good reproducibility, high specificity and acceptable method accuracy were acquired for the analysis of human serum specimens in liver cancer patients.


Assuntos
Biomarcadores Tumorais/sangue , Imunoensaio/métodos , Neoplasias Hepáticas/sangue , Nanoconjugados/química , Dióxido de Silício/química , alfa-Fetoproteínas/análise , Animais , Anticorpos Imobilizados/imunologia , Anticorpos Monoclonais/imunologia , Arginase/química , Arginina/química , Biomarcadores Tumorais/imunologia , Canavalia/enzimologia , Bovinos , Técnicas Eletroquímicas/métodos , Humanos , Limite de Detecção , Camundongos , Reprodutibilidade dos Testes , Urease/química , alfa-Fetoproteínas/imunologia
13.
J Biomed Opt ; 23(8): 1-12, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30112881

RESUMO

Constructing models of cells' realistic internal and external morphology is vital for correlation between light scattering and morphology of the scattering structure. The image stack obtained from fluorescent confocal microscopy is at present used to construct the cell's three-dimensional (3-D) morphology. However, due to the poor labeling quality and unavoidable optical noise present in the image stacks, 3-D morphologies are difficult to construct and are an impediment to the statistical analyses of cell structures. We propose a method called the "area and shape constraint method (ASCM)" for constructing 3-D morphology. Blurred 3-D morphologies constructed by common methods from image stacks considered as defective and which are commonly discarded are well restored by the ASCM. Seventy-four clinical blood samples and a series of standard fluorescent spheres are selected to evaluate the validity and precision of our proposed ASCM. Both the qualitative and quantitative results obtained by ASCM indicate the good performance of the method in constructing the cell's 3-D morphology.

14.
Drug Deliv ; 25(1): 1516-1525, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29968512

RESUMO

Gene delivery as a promising and valid tool has been used for treating many serious diseases that conventional drug therapies cannot cure. Due to the advancement of physical technology and nanotechnology, advanced physical gene delivery methods such as electroporation, magnetoporation, sonoporation and optoporation have been extensively developed and are receiving increasing attention, which have the advantages of briefness and nontoxicity. This review introduces the technique detail of membrane perforation, with a brief discussion for future development, with special emphasis on nanoparticles mediated optoporation that have developed as an new alternative transfection technique in the last two decades. In particular, the advanced physical approaches development and new technology are highlighted, which intends to stimulate rapid advancement of perforation techniques, develop new delivery strategies and accelerate application of these techniques in clinic.


Assuntos
Permeabilidade da Membrana Celular/fisiologia , Membrana Celular/genética , Membrana Celular/metabolismo , Técnicas de Transferência de Genes , Animais , Eletroporação/métodos , Técnicas de Transferência de Genes/tendências , Humanos
15.
Nanotechnology ; 29(35): 355704, 2018 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-29863482

RESUMO

Non-contact thermal sensors are important devices to study cellular processes and monitor temperature in vivo. Herein, a novel highly sensitive nanothermometer based on NaYF4:Yb,Er@ NaYF4@NaYF4:Yb,Tm@ NaYF4:Nd (denoted as Er@Y@Tm@Nd) was prepared by a facile solvothermal method. When excited by the near-infrared (NIR) light of 808 and 980 nm, the as-prepared Er@Y@Tm@Nd nanoparticles could emit both blue and green light, respectively, since the lanthanide cations responsible for these emissions are gathered inside this nanostructure. The green and blue light intensity ratio exhibits obvious temperature dependence in the range of the physiological temperature. Additionally, the fluorescence intensity of Er3+ and Tm3+ are also greatly enhanced due to the multilayer structure that implies avoiding the Er3+ and Tm3+ energy cross-relaxation by introduction of a NaYF4 wall between them. The as-prepared core-shell-shell-shell structure with Er3+ and Tm3+ in different layers improves dozens of times of the thermal sensitivity based on the non-thermal coupling levels of the probe: the maximum values for the sensitivity are 2.95% K-1 (I Er-521/I Tm-450) and 6.30% K-1 (I Tm-474/I Er-541) when excited by 980 and 808 nm laser sources, respectively. These values are well above those previously reported (<0.7% K-1), indicating that the prepared nanostructures are temperature sensors with excellent thermal sensitivity and sensitive to NIR wavelength excitation that makes them highly preferred for thermal detection.

16.
J Biomed Nanotechnol ; 14(8): 1430-1447, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29903058

RESUMO

The poor cell membrane penetration ability of photosensitizers resulted in the limited antitumor effect, thereby hampered their potential in clinical translation. The high toxic side effect and multidrug resistance of chemotherapeutic agents during in clinical chemical therapy should be resolved. Nanosystem integrated with photosensitizer and novel targeting chemotherapy agent may be an effective strategy for overcoming clinical or preclinical drawbacks of monotherapy and enhancing therapeutic effect. Therefore, a nanosized micelle F127 integrated with Apogossypolone (ApoG2) and Al(III) phthalocyanine chloride tetrasulfonic acid (AlPcS4) (referred as F127-ApoG2@AlPcS4) was synthesized to induce the cell death quickly for reducing the risk of resistance and enhancing gastric cancer therapeutic efficiency by combining AlPcS4/photodynamic therapy and ApoG2/chemotherapy. Hydrophobic of ApoG2 and hydrophilic of AlPcS4 self-assembled into this micelle to formation of core-shell structure based on the amphiphilic character of F127 micelle. The reactive oxygen species-dependent mitochondria membrane permeability was improved effectively because of reactive oxygen species generation of ApoG2, thereby resulting in a considerable amount of AlPcS4 and ApoG2 entering the mitochondrial. The AlPcS4 binding site was altered from the cytoplasm to the cell nucleus at higher concentration because of the existence of ApoG2. With irradiation, ApoG2 and AlPcS4 showed effective synergistic anti-tumor effect through inducing apoptosis due to singlet oxygen production regulated mainly by AlPcS4, reactive oxygen species accumulation and calcium overload regulated mainly by ApoG2. Intranuclear AlPcS4 caused cell death through necrosis. The apoptosis induced by AlPcS4 was earlier than ApoG2. In summary, F127-ApoG2@AlPcS4 quickly induced a long-lasting apoptosis that led to cell death, which could be a promising nanosized reagent for gastric cancer therapy based on chemo-photodynamic combined therapy.


Assuntos
Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Apoptose , Linhagem Celular Tumoral , Humanos , Nanotecnologia , Oxigênio Singlete
17.
Anal Bioanal Chem ; 410(16): 3723-3730, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29725730

RESUMO

By integrating imaging and drug-delivery in a single system, fluorescent nano-multifunctional imaging platforms can offer simultaneous diagnosis and therapy to diseases like cancer. However, the synthesis of such system involves a tedious, time-consuming, and multi-step process. Herein we report a facile method based on simple ultrasonication to synthesize highly cross-linked, monodispersed fluorescent polyphosphazene nanoparticles from hexachlorocyclotriphosphazene (HCCP) and dichlorofluorescein (FD). Various functional groups (folic acid, PEG-NH2, and methylene blue) can be "fastened" in situ onto the poly(cyclotriphosphazene-co-dichlorofluorescein) (PCTPDF) nanoparticles to expand its application as nano-multifunctional platform. All the nanoparticles were characterized spectrophotometrically, and morphology was established by the images obtained from scanning electron microscope (SEM). The synthesized multifunctional nanoparticles exhibited low toxicity and penetrated through the cytomembranes of human colon cancer (HCT 116) cells. When applied to in vivo tumor imaging using biologically engineered mouse model, methylene blue functionalized (PCTPDF@MB) nanoparticles exhibited excellent photodynamic activity and imaging ability. Thus, PCTPDF nanoplatform based on multi-functional fluorescent nanoparticles might offer an efficient solution to new age theranostics. Apart from diagnostics application, PCTPDF, as a nanoplatform, could also be utilized to achieve more comprehensive application in modern analytic chemistry. Graphical Abstract The table of contents.


Assuntos
Nanopartículas/química , Neoplasias/diagnóstico por imagem , Compostos Organofosforados/síntese química , Polímeros/síntese química , Animais , Fluorescência , Corantes Fluorescentes/química , Células HCT116 , Humanos , Camundongos , Camundongos Nus , Microscopia Confocal , Microscopia Eletrônica de Varredura , Neoplasias/tratamento farmacológico , Compostos Organofosforados/química , Fotoquimioterapia , Polímeros/química , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Nanomedicina Teranóstica
18.
Oncol Rep ; 40(1): 165-178, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29767247

RESUMO

Limited cellular delivery and internalization efficiency of Al(III) phthalocyanine chloride tetrasulfonic acid (AlPcS4) induce poor penetration ability in cells and a slight photodynamic therapy (PDT) effect on gastric cancer. The combination treatment of AlPcS4/PDT with low­dose chemotherapeutic agents may provide a promising treatment strategy to increase the weak delivery efficiency of AlPcS4, reducing the dose of chemical agents without reducing efficacy, and improving apoptosis­inducing abilities, thereby increasing the antitumor effects and decreasing the noxious side effects on gastric cancer. We investigated and compared the synergistic antitumor growth effect on gastric cancer cells by combining AlPcS4/PDT treatment with different low­dose chemotherapeutic agents, namely, 5­fluorouracil (5­FU), doxorubicin (DOX), cisplatin (CDDP), mitomycin C (MMC), and vincristine (VCR). The inhibitory effect was increased in treatments that combined AlPcS4/PDT with all the aforementioned low­dose chemotherapeutic agents, to a different extent. An evident synergistic effect was obtained in the combination treatment of AlPcS4/PDT with low­dose 5­FU, DOX, and MMC by increasing AlPcS4 intracellular uptake ability, improving apoptosis­inducing abilities, and prolonging apoptosis­inducing time. The low­dose chemotherapeutic agents prolonged the apoptosis­inducing period of AlPcS4/PDT, and AlPcS4/PDT quickly improved apoptosis­inducing abilities of chemotherapy even at low doses. Generally, the combination treatment of AlPcS4/PDT with low­dose chemotherapeutic agents had significant antitumor growth effects in addition to a low dark­cytotoxicity effect on gastric cancer, thereby representing an effective and feasible therapy method for gastric cancer.


Assuntos
Apoptose/efeitos dos fármacos , Indóis/farmacologia , Compostos Organometálicos/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Linhagem Celular Tumoral , Cisplatino/farmacologia , Terapia Combinada , Relação Dose-Resposta a Droga , Doxorrubicina/farmacologia , Sinergismo Farmacológico , Fluoruracila/farmacologia , Humanos , Mitomicina/farmacologia , Fotoquimioterapia , Neoplasias Gástricas/patologia , Vincristina/farmacologia
19.
Int J Nanomedicine ; 13: 2143-2160, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29692611

RESUMO

Purpose: Plasmonic nanostructure-mediated photothermal therapy (PTT) is a promising alternative therapy for the treatment of skin cancer and other diseases. However, the insufficient efficiency of PTT at irradiation levels tolerable to tissues and the limited biodegradability of nanomaterials are still crucial challenges. In this study, a novel nanosystem for PTT based on liposome-nanoparticle assemblies (LNAs) was established. Materials and methods: Thermal-sensitive liposomes (TSLs) encapsulating cantharidin (CTD) were coated with gold nanoparticles (GNPs) and used in near-infrared (NIR) illumination-triggered PTT and thermally induced disruption on A431 cells. Results: The coated GNPs disintegrated into small particles of 5-6 nm after disruption of TSLs, allowing their clearance by the liver and kidneys. CTD encapsulated in the TSLs was released into cytoplasm after PTT. The released CTD increased the apoptosis of PTT-treated tumor cells by blocking the heat shock response (HSR) and inhibiting the expression of HSP70 and BAG3 inhibiting the expression of HSP70 and BAG3 with the synergistic enhancement of CTD, the new nanosystem CTD-encapsulated TSLs coated with GNPs (CTD-TSL@GNPs) had an efficient PTT effect using clinically acceptable irradiation power (200 mW//cm2) on A431 cells. Conclusion: The developed CTD-TSL@GNPs may be a promising PTT agent for clinical skin cancer therapy.


Assuntos
Cantaridina/farmacologia , Lipossomos/química , Nanopartículas Metálicas/uso terapêutico , Fototerapia/métodos , Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/antagonistas & inibidores , Proteínas Reguladoras de Apoptose/metabolismo , Cantaridina/administração & dosagem , Cantaridina/química , Linhagem Celular Tumoral , Liberação Controlada de Fármacos , Ouro/química , Ouro/farmacologia , Proteínas de Choque Térmico HSP70/metabolismo , Humanos , Nanopartículas Metálicas/química
20.
Sci Total Environ ; 634: 141-149, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-29627536

RESUMO

A series of Mo2N/HZSM-5 and transition metal modified Mo2N/HZSM-5 catalysts were prepared for the catalytic upgrading of pine wood-derived pyrolytic vapors for the selective production of monocyclic aromatic hydrocarbons (MAHs), while restraining the formation of polycyclic aromatic hydrocarbons (PAHs). Pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) experiments were performed to determine the effects of several factors on selective MAHs production, including Mo2N loading on HZSM-5, transition metal (Fe, Ce, La, Cu, Cr) modification of Mo2N/HZSM-5, pyrolysis temperature, and catalyst-to-biomass ratio. In addition, quantitative experiments were conducted to determine the actual yields of major aromatic hydrocarbons and the source of aromatic hydrocarbons from basic biomass components. Results indicated that among the various catalysts, the Ce-10%Mo2N/HZSM-5 exhibited the best performance on promoting the formation of MAHs and restraining the generation of PAHs. Under the optimal conditions, the actual yields of MAHs and PAHs from Ce-10%Mo2N/HZSM-5 catalytic process were 99.8mg/g and 7.5mg/g, while those from HZSM catalyst were only 77.2mg/g and 23.7mg/g respectively. Furthermore, the possible catalytic mechanism of the Ce-Mo2N/HZSM-5 catalyst was proposed based on the catalyst characterization.

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