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2.
Sci Rep ; 14(1): 7847, 2024 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570595

RESUMO

Gastric cancer is a highly prevalent disease that poses a serious threat to public health. In clinical practice, gastroscopy is frequently used by medical practitioners to screen for gastric cancer. However, the symptoms of gastric cancer at different stages of advancement vary significantly, particularly in the case of early gastric cancer (EGC). The manifestations of EGC are often indistinct, leading to a detection rate of less than 10%. In recent years, researchers have focused on leveraging deep learning algorithms to assist medical professionals in detecting EGC and thereby improve detection rates. To enhance the ability of deep learning to detect EGC and segment lesions in gastroscopic images, an Improved Mask R-CNN (IMR-CNN) model was proposed. This model incorporates a "Bi-directional feature extraction and fusion module" and a "Purification module for feature channel and space" based on the Mask R-CNN (MR-CNN). Our study includes a dataset of 1120 images of EGC for training and validation of the models. The experimental results indicate that the IMR-CNN model outperforms the original MR-CNN model, with Precision, Recall, Accuracy, Specificity and F1-Score values of 92.9%, 95.3%, 93.9%, 92.5% and 94.1%, respectively. Therefore, our proposed IMR-CNN model has superior detection and lesion segmentation capabilities and can effectively aid doctors in diagnosing EGC from gastroscopic images.


Assuntos
Aprendizado Profundo , Neoplasias Gástricas , Humanos , Gastroscopia , Neoplasias Gástricas/diagnóstico por imagem , Gastroscópios
3.
Angew Chem Int Ed Engl ; 61(20): e202116909, 2022 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-35194913

RESUMO

Simultaneous imaging of multiple microRNAs (miRNAs) in individual living cells is challenging due to the lack of spectrally distinct encoded fluorophores and non-cytotoxic methods. We describe a multiplexed error-robust combinatorial fluorescent label-encoding method, termed fluorophores encoded error-corrected labels (FluoELs), enabling multiplexed miRNA imaging in living cells with error-correcting capability. The FluoELs comprise proportional dual fluorophores for encoding and a constant quantitative single fluorophore for error-corrected quantification. Both are embedded in 260 nm core-shell silica nanoparticles modified with molecular beacon detection probes. The FluoELs are low cytotoxic and could accurately quantify and spatially resolve nine breast-cancer-related miRNAs and evaluate their coordination. The FluoELs enabled a single-cell analysis platform to evaluate miRNA expression profiles and the molecular mechanisms underlying miRNA-associated diseases.


Assuntos
MicroRNAs , Linhagem Celular Tumoral , Corantes Fluorescentes , Humanos , MicroRNAs/análise , Sondas Moleculares , Análise de Célula Única
4.
Zhongguo Zhong Yao Za Zhi ; 46(22): 5819-5824, 2021 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-34951170

RESUMO

The freeze-drying technique, characterized by low-temperature processing, is especially suitable for sensitive volatile oils with thermal instability. However, there are few studies focusing on the retention of volatile oils in the processing of freeze-dried preparations. This study evaluated the effects of different addition methods(adsorption, emulsification, solid dispersion, and inclusion) on the retention rate of the main components in peppermint oil, aiming to explore the application feasibility of freeze-dried preparations of volatile oils. Firstly, the addition method was determined based on the retention rates of menthol in four freeze-dried preparations. Secondly, an orthogonal test was designed to optimize the preparation process based on the characteristics of the preferred addition method. The results showed that the most suitable preparation form of peppermint oil was inclusion with beta-cyclodextrin(ß-CD), and the retention rate of menthol in freeze-drying was 86.36%. According to the two-step preparation process of inclusion and freeze-drying, we introduced the product of inclusion rate and retention rate, i.e., comprehensive retention rate, to determine the optimum processing parameters. The results showed that ß-CD/oil ratio of 7∶1, inclusion temperature of 40 ℃, and inclusion time of 2 h were the optimum processing parameters. The product prepared with these parameter had the comprehensive retention rate of 68.41%, retention rate of 92.53%, and inclusion rate of 73.93%. The inclusion compound was white powder with significantly increased solubility. The pre-paration process based on cyclodextrin inclusion in this study is stable and reliable and provides a new idea for ensuring the efficacy and stability of volatile components in freeze-dried preparations.


Assuntos
Ciclodextrinas , Óleos Voláteis , Liofilização , Mentha piperita , Óleos de Plantas , Solubilidade , Tecnologia
5.
Adv Healthc Mater ; 10(21): e2101130, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34486246

RESUMO

The aberrant expression level of intracellular microRNAs (miRNAs) holds great promise for differentiating cell types at the molecular level. However, cell subtype discrimination based on a single miRNA molecular level is not sufficient and reliable. Herein, multiple identifiable and reporting modules are integrated into a single DNA circuit for multiple cancer cell subtypes identification based on miRNAs bispecific recognition. The DNA three-dimensional (3D) logic gate nano-hexahedron framework extends three recognition modules and three reporting modules to form three "AND" logic gates. Each Boolean operator "AND" returns an "ON" signal in the presence of bispecific miRNAs, simultaneously enabling three types of cell subtype identification. It not only enables the discrimination of cancer cells A549 and MCF-7 from normal cells NHDF but also successfully distinguishes different types of cancer cells. The bispecific intracellular miRNA controllable DNA circuit, with low signal-to-noise ratio, easily extends to various cell type discrimination by adjusting the miRNA species, provides huge opportunities for accurately differentiating multiple cell types at the molecular level.


Assuntos
Computadores Moleculares , MicroRNAs , Células A549 , DNA , Humanos , Lógica , Células MCF-7 , Nanotecnologia
6.
Zhongguo Zhong Yao Za Zhi ; 46(15): 3949-3959, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34472272

RESUMO

Qishen Yiqi Dripping Pills(QSYQ) are used clinically to treat various myocardial ischemic diseases, such as angina pectoris, myocardial infarction, and heart failure; however, the molecular mechanism of QSYQ remains unclear, and the scientific connotation of traditional Chinese medicine(TCM) compatibility has not been systematically explained. The present study attempted to screen the critical pathway of QSYQ in the treatment of myocardial ischemia by network pharmacology and verify the therapeutic efficacy with the oxygen-glucose deprivation(OGD) model, in order to reveal the molecular mechanism of QSYQ based on the critical pathway. The key targets of QSYQ were determined by active ingredient identification and target prediction, and underwent pathway enrichment analysis and functional annotation with David database to reveal the biological role and the critical pathway of QSYQ. Cell counting Kit-8(CCK-8), lactate dehydrogenase(LDH), and Western blot tests were launched on high-content active ingredients with OGD cell model to reveal the molecular mechanism of QSYQ based on the critical pathway. The results of network pharmacology indicated that QSYQ, containing 18 active ingredients and 82 key targets, could protect cardiomyocytes by regulating biological functions, such as nitric oxide biosynthesis, apoptosis, inflammation, and angiogenesis, through TNF signaling pathway, HIF-1 signaling pathway, PI3 K-Akt signaling pathway, etc. HIF-1 signaling pathway was the critical pathway. As revealed by CCK-8 and LDH tests, astragaloside Ⅳ, salvianic acid A, and ginsenoside Rg_1 in QSYQ could enhance cell viability and reduce LDH in the cell supernatant in a concentration-dependent manner(P<0.05). As demonstrated by the Western blot test, astragaloside Ⅳ significantly down-regulated the protein expression of serine/threonine-protein kinase(Akt1) and hypoxia-inducible factor 1α(HIF-1α) in the HIF-1 signaling pathway, and up-regulated the protein expression of vascular endothelial growth factor A(VEGFA). Salvianic acid A significantly down-regulated the protein expression of upstream phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3 CA) and downstream HIF-1α of Akt1. Ginsenoside Rg_1 significantly down-regulated the expression of HIF-1α protein and up-regulated the expression of VEGFA. The therapeutic efficacy of QSYQ on myocardial ischemia was achieved by multiple targets and multiple pathways, with the HIF-1 signaling pathway serving as the critical one. The active ingredients of QSYQ could protect cardiomyocytes synergistically by regulating the targets in the HIF-1 signaling pathway to inhibit its expression.


Assuntos
Medicamentos de Ervas Chinesas , Isquemia Miocárdica , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/genética , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular
7.
J Ethnopharmacol ; 278: 114283, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34098017

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Gegen Qinlian Decoction (GQD) (including: Puerariae lobatae (Willd.) Ohwi, radix; (short for Gengen) Glycyrrhiza uralensis Fisch., root and rhizome (short for Gancao), honeyed; Coptis chinensis Franch., rhizome (short for Huanglian); Scutellaria baicalensis Georgi, radix, boiled (short for S. baicalensis) has been widely used to treat inflammatory bowel disease (IBD) and colorectal cancer (CRC). To explore compatibility mechanism of GQD could be of advantage to investigate the complex principle of TCM, which might be conducive to the exploration of the modernization of TCM. AIM OF REVIEW: In this study, a strategy based on system pharmacology was constructed to uncover the multi-target regulation and compatibility mechanism of GQD on the Wnt signaling pathways. MATERIAL AND METHODS: The pharmacological network of GQD was constructed by TCMSP, DAVID, Uniprote database. The cell growth inhibitory effects of puerarin (PUE), wogonin (WOG), berberine (BER), and glycyrrhetinic acid (GLY) on SW480 cells were assessed using CCK-8 assay. The multi-target regulation and compatibility mechanism of combination PUE with GLY were examined by RNA-seq, HPLC-QQQ/MS, qRT- PCR and Western blot analysis. RESULTS: Network pharmacology analysis indicated that PUE, WOG, BER and GLY were the active components in GQD and had a synergistic effect on the targets of the Wnt signaling pathway. Additionally, pharmacological experiments revealed that WOG, BER, and GLY inhibited activity of colorectal cancer (CRC) cell lines SW480 cells, and that PUE only exhibited effective antitumour activity when combined with GLY. CTNNB1, CCND1 and SMAD4 were identified as synergistic targets inhibited by PUE-GLY. Moreover, PUE-GLY could influence the Wnt signaling pathway by upregulating GSK3B and downregulating CTNNB1 synergistically. It also showed that GLY could effectively increase the intracellular content of PUE based on HPLC-QQQ/MS analysis, and this process was achieved by influencing the targets of the membrane's pathway, such as cell adhesion molecules, focal adhesion, and tight junctions. CONCLUSION: GLY was revealed a multi-target mechanism, which could downregulate CTNNB1 as the active component and intervene in membrane proteins (CDH1, CADM1, ITGB2, ICAM1, ITGA1) as 'guide' in the formulae. Moreover, the mechanism of synergistic antitumour action of PUE (the active component of Monarch drug) and GLY (the active component of Guide drug) on the Wnt signaling pathway was explored systematically. It was a promising breakthrough for elucidating the scientific connotation of the compatibility of TCM formulae and provide a valuable and practicable methodology for clarifying the mechanisms of TCM.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Via de Sinalização Wnt/efeitos dos fármacos , Linhagem Celular Tumoral , Sinergismo Farmacológico , Humanos , Farmacologia em Rede , RNA-Seq
8.
Nanoscale ; 13(5): 3049-3060, 2021 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-33514969

RESUMO

The development of a simple and effective single constituent multifunctional nanotheranostic platform producing a multimodality diagnostic signal and curing effect is still a challenge. Herein, we synthesized simple and biodegradable FeWOx ternary oxide nanoparticles and modified their surface with RGD-PEG-NH2 (FeWOx-PEG-RGD NPs), whereby resulting NPs possessed a (T2/T1) switchable MRI/CT dual-modal imaging ability and synergistic photothermal therapy (PTT)/photodynamic therapy (PDT)/chemodynamic therapy (CDT) capacity. We showed that FeWOx-PEG-RGD NPs enabled tumor accumulation under a magnetic field drive and RGD-mediated tumor penetration and implemented PTT/PDT treatment under 980 nm laser irradiation. In an acidic tumor microenvironment (TME) with a high hydrogen peroxide (H2O2) expression, NPs degraded to release Fe3+ and Fe2+, triggering a Fenton reaction to generate ˙OH for CDT. The released Fe2+ led to T2/T1 signal conversion for tracing cancer therapy, while the high X-ray attenuation coefficient of W also made it a good CT contrast agent for guided therapy. Thus, the structurally simple FeWOx-PEG-RGD was capable of mediating (T2/T1-weighted) MR/CT two modal imaging-guided PTT/PDT/CDT synergic therapy with a high accuracy and superb anticancer efficiency. The simple, degradable, rapid-clearance, and multifunctional FeWOx-PEG-RGD NPs provide a novel, promising, and versatile nanotheranostic platform.


Assuntos
Peróxido de Hidrogênio , Nanopartículas , Linhagem Celular Tumoral , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X
9.
Anal Chim Acta ; 1139: 164-168, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33190700

RESUMO

Fluorescence quenching property of two-dimensional (2D) nanosheets (NSs) have received extensively attention in the construction of novel biosensing platform. However, the heterogeneity of the wide-size distribution and inefficient fluorescence quenching capacity limit its wide practical applications. Herein, for the first time, we report a novel fluorescent biosensor based on uniform palladium NSs (Pd NSs) with excellent fluorescence quenching efficiency and differential affinity toward ssDNA versus dsDNA and combination with a pair of DNA detection probes with fluorophore for detecting circulating tumor DNA (ctDNA). The DNA detection probes are facilitated to adsorbed to the surface of Pd NSs, leading to efficient fluorescence quench. In the presence of target DNA, it can be linked by T4 DNA ligase to form long DNA duplex structures, which display weak affinity toward Pd NSs, producing the fluorescence recovery. The remarkable fluorescence quenching efficiency and ssDNA/dsDNA differential affinity of Pd NSs make it have a good detection ability without signal amplification. The result indicates that this facile but cost-effective strategy holds great promise in bioanalysis.


Assuntos
Técnicas Biossensoriais , DNA Tumoral Circulante , Sondas de DNA , Fluorometria , Paládio
10.
Zhongguo Zhong Yao Za Zhi ; 45(8): 1772-1778, 2020 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-32489060

RESUMO

Wogonin is a main effective component of Scutellaria baicalensis, with a significant anti-cancer activity. Recently, extensive studies focused on anti-cancer pharmacological effects of wogonin, but there were still a few studies on its molecular mechanism. Therefore, the molecular targets of its anti-cancer activity were still unclear. In this study, network pharmacology was applied to investigate the potential targets and molecular pathway of wogonin in inhibiting the growth of colorectal cancer. It indicated that Wnt/ß-catenin was a key pathway of wogonin on colorectal cancer. Then, pharmacology and molecular mechanism studies were performed according to network pharmacological results. Pharmacological results revealed that wogonin inhibited significantly the proliferation of SW480(P<0.001), with a concentration-dependent regularity in the range of 12.5-50 µmol·L~(-1). Additionally, wogonin could induce G_1 phase blocking of SW480 cells. Western blot was used to investigate the effect of wogonin on four characteristic proteins of Wnt/ß-catenin pathway. CTNNB1(ß-catenin), BIRC5(survivin) and GSK3 B were down-regulated significantly, while the expression level of BAX was up-regulated(P<0.05). In conclusion, wogonin could inhibit the proliferation of SW480 cells through Wnt/ß-catenin pathway. The feature protein CTNNB1(ß-catenin), BIRC5(survivin), GSK3 B and BAX were identified as the potential targets. This study illuminated the anti-cancer molecular mechanism and drug targets of wogonin, which provided a theoretical basis for anti-colon cancer drug discovery and clinical application.


Assuntos
Neoplasias Colorretais , Quinase 3 da Glicogênio Sintase , Linhagem Celular Tumoral , Proliferação de Células , Flavanonas , Humanos , Via de Sinalização Wnt , beta Catenina
11.
Nat Commun ; 11(1): 1735, 2020 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-32269223

RESUMO

The therapeutic effect of reactive oxygen species (ROS)-involved cancer therapies is significantly limited by shortage of oxy-substrates, such as hypoxia in photodynamic therapy (PDT) and insufficient hydrogen peroxide (H2O2) in chemodynamic therapy (CDT). Here, we report a H2O2/O2 self-supplying nanoagent, (MSNs@CaO2-ICG)@LA, which consists of manganese silicate (MSN)-supported calcium peroxide (CaO2) and indocyanine green (ICG) with further surface modification of phase-change material lauric acid (LA). Under laser irradiation, ICG simultaneously generates singlet oxygen and emits heat to melt the LA. The exposed CaO2 reacts with water to produce O2 and H2O2 for hypoxia-relieved ICG-mediated PDT and H2O2-supplying MSN-based CDT, acting as an open source strategy for ROS production. Additionally, the MSNs-induced glutathione depletion protects ROS from scavenging, termed reduce expenditure. This open source and reduce expenditure strategy is effective in inhibiting tumor growth both in vitro and in vivo, and significantly improves ROS generation efficiency from multi-level for ROS-involved cancer therapies.


Assuntos
Tratamento Farmacológico , Fotoquimioterapia , Espécies Reativas de Oxigênio/metabolismo , Animais , Circulação Sanguínea , Compostos de Cálcio/química , Linhagem Celular Tumoral , Sobrevivência Celular , Sinergismo Farmacológico , Feminino , Humanos , Peróxido de Hidrogênio/metabolismo , Verde de Indocianina/química , Ácidos Láuricos/sangue , Ácidos Láuricos/química , Imageamento por Ressonância Magnética , Manganês/química , Camundongos Endogâmicos BALB C , Nanopartículas/química , Nanopartículas/ultraestrutura , Óxidos/química , Silicatos/química , Superóxidos/metabolismo , Distribuição Tecidual
12.
Anal Chem ; 92(6): 4411-4418, 2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-32056432

RESUMO

Quantifying intracellular microRNA (miRNA) is essential for diagnosis and prognosis of diseases because of its importance to the development and progression of complex diseases. The challenge is to develop methods that enable multiplex miRNAs detection in ultralow amounts and over broad concentration ranges. Inspired by the "tentacles" of an octopus, herein, we present a framework nucleic acid (FNA) capture for sensitive, rapid, and multiplexed imaging of miRNAs cancer biomarkers in living cells. The programmable FNA is designed using three DNA triangular prism (DTP) nanostructures carrying two pairs of metastable catalytic hairpin assembled (CHA) probes, AS1411 aptamer, and pendent biotinylated DNA strand in different vertexes and is further assembled via streptavidin to form the multivalent DTP (SA-DTP). The SA-DTP system acts as an octopus that captures the target cancer miRNAs quickly and delivers them preferentially among DTPs' "tentacles" in the SA-DTP system to produce strong, amplified fluorescence for detection. Precise multiplexed imaging of miRNA-155 and miRNA-21 cancer biomarkers' aberrant expression and dynamic change in different cells demonstrates the feasibility of both monitoring disease progression and evaluating therapeutic efficacy.


Assuntos
Biomarcadores Tumorais/análise , DNA/química , MicroRNAs/análise , Nanoestruturas/química , Humanos , Células MCF-7 , Imagem Óptica
13.
Angew Chem Int Ed Engl ; 59(16): 6601-6606, 2020 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-31994305

RESUMO

The two-dimensional (2D) vanadium carbide (V2 C) MXene has shown great potential as a photothermal agent (PTA) for photothermal therapy (PTT). However, the use of V2 C in PTT is limited by the harsh synthesis condition and low photothermal conversion efficiency (PTCE). Herein, we report a completely different green delamination method using algae extraction to intercalate and delaminate V2 AlC to produce mass V2 C nanosheets (NSs) with a high yield (90 %). The resulting V2 C NSs demonstrated good structural integrity and remarkably high absorption in near infrared (NIR) region with a PTCE as high as 48 %. Systemic in vitro and in vivo studies demonstrate that the V2 C NSs can serve as efficient PTA for photoacoustic (PA) and magnetic resonance imaging (MRI)-guided PTT of cancer. This work provides a cost-effective, environment-friendly, and high-yielding disassembly approach of MAX, opening a new avenue to develop MXenes with desirable properties for a myriad of applications.


Assuntos
Raios Infravermelhos , Nanoestruturas/química , Fármacos Fotossensibilizantes/química , Vanádio/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Humanos , Células MCF-7 , Camundongos , Camundongos Nus , Nanoestruturas/uso terapêutico , Nanoestruturas/toxicidade , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Fármacos Fotossensibilizantes/metabolismo , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fototerapia , Nanomedicina Teranóstica , Distribuição Tecidual , Transplante Heterólogo
14.
Adv Healthc Mater ; 9(2): e1901528, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31820854

RESUMO

Bimetallic nanoparticles have received considerable attention owing to synergistic effect and their multifunctionality. Herein, new multifunctional Pd@Au bimetallic nanoplates decorated hollow mesoporous MnO2 nanoplates (H-MnO2 ) are demonstrated for achieving not only nucleus-targeted NIR-II photothermal therapy (PTT), but also tumor microenvironment (TME) hypoxia relief enhanced photodynamic therapy (PDT). The Pd@Au nanoplates present a photothermal conversion efficiency (PTCE) as high as 56.9%, superior to those PTAs activated in the NIR-II region such as Cu9 S5 nanoparticles (37%), Cu3 BiS3 nanorods (40.7%), and Au/Cu2-x S nanocrystals (43.2%). They further functionalize with transactivator of transcription (TAT) moiety for cell nuclear-targeting and biodegradable hollow mesoporous MnO2 (≈100 nm) loaded with photosensitizer Ce6 (TAT-Pd@Au/Ce6/PAH/H-MnO2 ) to construct a hierarchical targeting nanoplatform. The as-made TAT-Pd@Au/Ce6/PAH/H-MnO2 demonstrates good premature renal clearance escape ability and increased tumor tissue accumulation. It can be degraded in acidic TME and generate O2 by reacting to endogenous H2 O2 to relieve the hypoxia for enhanced PDT, while the released small TAT-Pd@Au nanoplates can effectively enter into the nucleus to mediate PTT. As a result, a remarkable therapeutic effect is achieved owing to the synergistic PTT/PDT therapy. This hierarchical targeting, TME-responsive, cytoplasm hypoxia relief PDT, and nuclear NIR-II PTT synergistic therapy can pave a new avenue for nanomaterials-based cancer therapy.


Assuntos
Nanopartículas Metálicas/química , Fotoquimioterapia/métodos , Terapia Fototérmica/métodos , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacologia , Feminino , Ouro/química , Humanos , Peróxido de Hidrogênio/química , Células MCF-7 , Compostos de Manganês/química , Camundongos Endogâmicos BALB C , Nanopartículas Multifuncionais , Óxidos/química , Oxigênio/farmacocinética , Paládio/química , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Nanomedicina Teranóstica/métodos , Hipóxia Tumoral/efeitos dos fármacos , Microambiente Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Biomater Sci ; 7(12): 5084-5096, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31565707

RESUMO

A dual function system that inhibits tumor growth while promoting wound healing is very necessary for melanoma treatment since tumor killing and skin healing are two complementary and influential processes. Herein, a controllable local drug delivery system based on porous fiber membranes incorporated with CuS nanoparticles is designed for chemo-photothermal synergistic melanoma therapy and promoting wound healing. The porous structure on the fiber surface significantly increases the drug loading capacity of the membrane and the photothermal effect of incorporated CuS nanoparticles is used to control the drug release rate. Benefitting from the chemo-photothermal synergistic therapy, the composite membrane can effectively kill melanoma cells in vitro and inhibit tumor growth in vivo. Furthermore, the membrane can also significantly promote the cutaneous wound healing by providing mechanical support and releasing copper ions. Thus, this work provides new ideas for the development of multifunctional local treatment and postoperative care systems.


Assuntos
Cobre/administração & dosagem , Doxiciclina/administração & dosagem , Melanoma/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Animais , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cobre/química , Cobre/farmacologia , Modelos Animais de Doenças , Doxiciclina/química , Doxiciclina/farmacologia , Sistemas de Liberação de Medicamentos , Feminino , Membranas Artificiais , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/química , Fotoquimioterapia , Porosidade , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Anal Chem ; 91(15): 9828-9835, 2019 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-31282147

RESUMO

There is intense interest in visualizing intracellular microRNA (miRNA) in situ due to its valuable diagnostic and prognostic function and expressional heterogeneity. The direct monitoring of intracellular miRNA expressional level with a wide concentration range and in ultralow amount remains a key challenge. Herein, we report a responsive DNA "nano wheel" (DNW) by hybridization of modified six DNA hairpin structures to a programmed DNA nanowire for highly efficient and fast miRNA imaging in living cells. We demonstrate that one target miRNA is able to trigger the nearby DNA hairpins sequential hybridization through accelerated localized DNA cascade reaction (LDCR) along the DNA nanowire and open of the self-quenched hairpins to assemble six-arm branched junction "nano wheel" structure lighted with three fluorescence dye. Notably, the recycled miRNA target further acts as an catalyst to generate multiple lighted "nano wheel" structures, thus one target miRNA enable to trigger strong and amplified fluorescence signal for intracellular sensitive imaging. Meanwhile, the LDCR endows the system with fast reaction kinetics owing to the high local concentration. It outperforms the "one-to-one" conventional molecular beacon (MB) and intermolecular hybridization-based six-arm branched junction in sensitivity and reaction kinetics for intracellular miRNA imaging verified using MCF-7, A549, Hela, and NHDF cells. The programmed DNW provides a useful and valuable tool for rapid and highly efficient visualization of low-abundance miRNA in living cells, which is beneficial to understand the miRNA function and exploration of its biomedical application.


Assuntos
DNA/química , Espaço Intracelular/metabolismo , MicroRNAs/metabolismo , Nanoestruturas/química , Linhagem Celular Tumoral , Humanos , Cinética , Hibridização de Ácido Nucleico
17.
ACS Nano ; 13(4): 4267-4277, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-30901515

RESUMO

The integration of reactive oxygen species (ROS)-involved photodynamic therapy (PDT) and chemodynamic therapy (CDT) holds great promise for enhanced anticancer effects. Herein, we report biodegradable cancer cell membrane-coated mesoporous copper/manganese silicate nanospheres (mCMSNs) with homotypic targeting ability to the cancer cell lines and enhanced ROS generation through singlet oxygen (1O2) production and glutathione (GSH)-activated Fenton reaction, showing excellent CDT/PDT synergistic therapeutic effects. We demonstrate that mCMSNs are able to relieve the tumor hypoxia microenvironment by catalytic decomposition of endogenous H2O2 to O2 and further react with O2 to produce toxic 1O2 with a 635 nm laser irradiation. GSH-triggered mCMSNs biodegradation can simultaneously generate Fenton-like Cu+ and Mn2+ ions and deplete GSH for efficient hydroxyl radical (•OH) production. The specific recognition and homotypic targeting ability to the cancer cells were also revealed. Notably, relieving hypoxia and GSH depletion disrupts the tumor microenvironment (TME) and cellular antioxidant defense system, achieving exceptional cancer-targeting therapeutic effects in vitro and in vivo. The cancer cells growth was significantly inhibited. Moreover, the released Mn2+ can also act as an advanced contrast agent for cancer magnetic resonance imaging (MRI). Thus, together with photosensitizers, Fenton agent provider and MRI contrast effects along with the modulating of the TME allow mCMSNs to realize MRI-monitored enhanced CDT/PDT synergistic therapy. It provides a paradigm to rationally design TME-responsive and ROS-involved therapeutic strategies based on a single polymetallic silicate nanomaterial with enhanced anticancer effects.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Cobre/uso terapêutico , Manganês/uso terapêutico , Nanosferas/uso terapêutico , Silicatos/uso terapêutico , Células A549 , Animais , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Feminino , Glutationa/metabolismo , Humanos , Células MCF-7 , Camundongos Nus , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Hipóxia Tumoral/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos
18.
Chem Sci ; 10(6): 1709-1715, 2019 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-30842835

RESUMO

Mature microRNAs (miRNAs) produced from precursor microRNAs (pre-miRNAs) by the RNase Dicer have showed significant potential for cancer diagnosis and prognosis due to their key regulatory roles in various pathological processes. However, discriminatory detection of low-abundance miRNAs and pre-miRNAs remains a key challenge since the mature sequence is also present in the pre-miRNA forms. Herein, we report a novel cascade reaction to sensitively distinguish miRNAs versus pre-miRNAs in living cells based on two pairs of programmable hairpin oligonucleotide probes with a simple sequence design. The programmable hairpin probes can metastably coexist until the introduction of miRNAs or pre-miRNAs, which can trigger a specific hybridization chain reaction (HCR), respectively, leading to the self-assembly of nicked DNA duplex structures and a remarkable specific fluorescence intensity increase. The system can readily and sensitively assess the miRNA or pre-miRNA abundance in a homogeneous solution. The intracellular miRNA and pre-miRNA expression level assessment in different living cells is realized. Thus, we provide a novel investigation tool for discriminatorily and accurately assessing miRNA and pre-miRNA abundance, which could be useful for the biomedical application of miRNAs.

19.
Adv Mater ; 31(12): e1807888, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30730070

RESUMO

Herein, a cancer cell (MCF-7 cell) membrane-encapsulated dendritic mesoporous silica nanoparticle simultaneously functionalized with DNA-photoacoustic (DNA-PA) probes and glutathione (GSH)-responsive DNA fuel strands for PA imaging of tumor-related miRNA in living mice with signal amplification ability is developed. It is demonstrated that one target miRNA can trigger disassembly of multiple PA fluorophore probes from the quencher with the aid of GSH-responsive DNA fuel strands via the entropy-driven process, resulting remarkable amplified change of PA signal ratio. Using oncogenic miRNA-21 as a model, a linear relationship between miRNA-21 concentrations and PA ratio in a dynamic range from 10 × 10-12 m to 100 × 10-9 m and a limit of detection down to 11.69 × 10-12 m are established. The accurate PA signal observation related to miRNA-21s in the tumor area in living mice is demonstrated, and the PA signal ratio increases significantly via the injection of miRNA-21. It is anticipated that the catalytic ratiometric PA imaging system can be applied to an array of molecular detection in living system by rational detection probe design.


Assuntos
Membrana Celular/metabolismo , Indicadores e Reagentes/química , MicroRNAs/análise , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Técnicas Fotoacústicas/métodos , Animais , Catálise , Sondas de DNA/química , Corantes Fluorescentes/química , Glutationa/química , Humanos , Células MCF-7 , Camundongos , MicroRNAs/metabolismo , Tamanho da Partícula , Porosidade , Dióxido de Silício/química , Propriedades de Superfície
20.
Nano Lett ; 19(2): 1179-1189, 2019 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-30640481

RESUMO

Developing nanophotothermal agents (PTAs) with satisfied photothermal conversion efficiency (PTCE) in the second NIR window (1000-1350 nm, NIR II) holds great promise for enhanced photothermal therapy effect. Herein, we develop a NIR-II PTA with advanced PTCE, based on a new two-dimensional ultrathin tellurium oxide/ammonium tungsten bronze (TeO2/(NH4) xWO3) nanoribbons (TONW NRs). The doped ammonia ions-mediated-free-electrons injection into the lowest unoccupied molecular orbital band of WO3 combined with the electronic transitions between W6+ ions and the lone pair of electrons in Te atoms achieve excellent NIR absorption of TONW NRs resulting from localized surface plasmon resonance. The polyethylene glycol functionalized TONW NRs (PEG-TONW NRs) exhibit good stability and biocompatibility, displaying a PTCE high to 43.6%, surpassing many previous nano-PTAs active in the NIR II region, leading to remarkable tumor ablation ability both in vitro and in vivo. Meanwhile, advanced X-ray computed tomography (CT) and photoacoustic (PA) imaging capability of PEG-TONW NRs were also realized. Given the admirable photothermal effect in NIR II region, good biocompatibility, and advanced CT/PA imaging diagnosis capability, the novel PEG-TONW NRs is promising in future personalized medicine applications.

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