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1.
Nanotechnology ; 32(45)2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34340227

RESUMO

In this study, a nanodrug carrier (mesoporous silica nanoparticle (MSN)-SS-cysteamine hydrochloride (CS)-hyaluronic acid (HA)) for targeted drug delivery was prepared using MSNs, in which HA was used as a targeting ligand and blocking agent to control drug release. Coumarin is a fluorescent molecule that targets mitochondria. Two conjugates (XDS-DJ and 5-FUA-4C-XDS) were synthesized by chemically coupling nitrogen mustard and 5-fluorouracil with coumarin, which was further loaded into MSN-SS-CS-HA nanocarriers. MTT analysis demonstrated that the nanocomposite MSN-SS-CS@5-FUA-4C-XDS/HA displayed stronger cytotoxicity toward HCT-116 cells than HeLa or QSG-7701 cells. Furthermore, MSN-SS-CS@5-FUA-4C-XDS/HA was able to target the mitochondria of HCT-116 cells, causing decreased mitochondrial membrane potential and excessive production of reactive oxygen species. These results indicate that MSN-SS-CS@5-FUA-4C-XDS/HA has the potential to be a nanodrug delivery system for the treatment of colon cancer.


Assuntos
Cumarínicos/síntese química , Cisteamina/química , Fluoruracila/química , Ácido Hialurônico/química , Mitocôndrias/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cumarínicos/química , Cumarínicos/farmacologia , Composição de Medicamentos , Células HCT116 , Células HeLa , Humanos , Mecloretamina/química , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Nanopartículas , Tamanho da Partícula , Porosidade , Espécies Reativas de Oxigênio/metabolismo , Dióxido de Silício , Nanomedicina Teranóstica
2.
Langmuir ; 33(27): 6727-6731, 2017 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-28657319

RESUMO

Surfaces with gradient properties are of central importance for a number of chemical and biological processes. Here, we report rapid generation of a polydopamine (PDA) gradient on hydrophobic surfaces by a simple, low cost, and general technology, cyclic draining-replenishing (CDR). Due to the unique surface chemistry of PDA, it enables continuous and precise control of surface wettability and subsequent deposition of organic and inorganic compounds. Using kanamycin as a model compound, we show that the gradient PDA membrane potentially can be used to prepare minimum inhibitory concentration (MIC) test strips for quantifying resistance of antimicrobial agents from microorganisms. Because CDR is experimentally simple, scalable, fast, and does not require specialized reagents or instruments, we envision this platform can be easily adopted to create a variety of functional surfaces.


Assuntos
Indóis/química , Polímeros/química , Anti-Infecciosos , Molhabilidade
3.
Acta Biomater ; 180: 394-406, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38615810

RESUMO

The construction and optimization of a single phototherapeutic agent with photoluminescence, type I photodynamic therapy (PDT), and photothermal therapy (PTT) functions remain challenging. In this study, we aimed to design and synthesize four donor-acceptor (D-A) type aggregation-induced emission molecules: PSI, TPSI, PSSI, and TPSSI. We employed phenothiazine as an electron donor and 1,3-bis(dicyanomethylidene)indan as a strong electron acceptor in the synthesis process. Among them, TPSSI exhibited efficient type I reactive oxygen species generation, high photothermal conversion efficiency (45.44 %), and near-infrared emission. These observations can be attributed to the introduction of a triphenylamine electron donor group and a thiophene unit, which resulted in increased D-A strengths, a reduced singlet-triplet energy gap, and increased free intramolecular motion. TPSSI was loaded into bovine serum albumin to prepare biocompatible TPSSI nanoparticles (NPs). Our results have indicated that TPSSI NPs can target lipid droplets with negligible dark toxicity and can efficiently generate O2•- in hypoxic tumor environments. Moreover, TPSSI NPs selectively targeted 4T1 tumor tissues and exhibited a good PDT-PTT synergistic effect in vitro and in vivo. We believe that the successful preparation of multifunctional phototherapeutic agents will promote the development of efficient tumor diagnosis and treatment technologies. STATEMENT OF SIGNIFICANCE: The construction of a single phototherapeutic agent with photoluminescence, type I photodynamic therapy, and photothermal therapy functions, and its optimization remain challenging. In this study, we construct four donor-acceptor aggregation-induced emission molecules using phenothiazine as an electron donor and 1,3-Bis(dicyanomethylidene)indan as a strong electron acceptor. By optimizing the molecular structure, an integrated phototherapy agent with fluorescence imaging ability and high photodynamic / photothermal therapy performance was prepared. We believe that the successful preparation of multifunctional phototherapeutic agents will promote the development of efficient tumor diagnosis and treatment technology.


Assuntos
Fotoquimioterapia , Terapia Fototérmica , Animais , Fotoquimioterapia/métodos , Camundongos , Feminino , Camundongos Endogâmicos BALB C , Linhagem Celular Tumoral , Raios Infravermelhos , Nanopartículas/química , Nanopartículas/uso terapêutico
4.
Chemosphere ; 359: 142324, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38740339

RESUMO

Seawater warming, ocean acidification and chemical pollution are the main threats to coral growth and even survival. The legacy persistent organic contaminants (POCs), such as polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs), and the emerging contaminants, including polybrominated diphenyl ethers (PBDEs), dechlorane plus (DPs) and novel brominated flame retardants (NBFRs) were studied in corals from Luhuitou fringing reef in Sanya Bay and Yongle atoll in Xisha Islands, the South China Sea (SCS). Total average concentrations of ∑16PAHs, ∑23OCPs, ∑34PCBs, ∑8PBDEs, ∑2DPs and ∑5NBFRs in 20 coral species (43 samples) from the SCS were 40.7 ± 34.6, 5.20 ± 5.10, 0.197 ± 0.159, 3.30 ± 3.70, 0.041 ± 0.042 and 36.4 ± 112 ng g-1 dw, respectively. PAHs and NBFRs were the most abundant compounds and they are likely to be dangerous pollutants for future coral growth. Compared to those found in other coral reef regions, these pollutants concentrations in corals were at low to median levels. Except for PBDEs, POCs in massive Porites were significantly higher than those in branch Acropora and Pocillopora (p < 0.01), as large, closely packed corals may be beneficial for retaining more pollutant. The current study contributes valuable data on POCs, particularly for halogenated flame retardants (HFRs, including PBDEs, DPs and NBFRs), in corals from the SCS, and will improve our knowledge of the occurrence and fate of these pollutants in coral reef ecosystems.


Assuntos
Antozoários , Monitoramento Ambiental , Retardadores de Chama , Éteres Difenil Halogenados , Hidrocarbonetos Clorados , Poluentes Orgânicos Persistentes , Bifenilos Policlorados , Hidrocarbonetos Policíclicos Aromáticos , Água do Mar , Poluentes Químicos da Água , Animais , Hidrocarbonetos Policíclicos Aromáticos/análise , Poluentes Químicos da Água/análise , China , Éteres Difenil Halogenados/análise , Retardadores de Chama/análise , Água do Mar/química , Bifenilos Policlorados/análise , Hidrocarbonetos Clorados/análise , Praguicidas/análise , Recifes de Corais , Oceanos e Mares
5.
Yao Xue Xue Bao ; 48(4): 566-72, 2013 Apr.
Artigo em Zh | MEDLINE | ID: mdl-23833947

RESUMO

The gamma-cyclodextrin-folate (gamma-CD/FA) inclusion-coated CdSe/ZnS quantum dots (QDs) with folate-receptor (FR) targeted were synthesized by simple and convenient sonochemical method. The products were studied using Fourier transform infrared (FTIR), proton nuclear magnetic resonance (1H NMR), utraviolet-visible spectrometry (UV-vis), fluorescence spectrum and transmission electron micrographs (TEM). The results showed that the gamma-CD/FA-coated CdSe/ZnS QDs not only have good monodispersity and smaller size, but also have good optical performance, such as higher quantum yield (QY) and a long fluorescence lifetime. The cytotoxicity experiments showed that the gamma-CD/FA-coated CdSe/ZnS QDs have lower cytotoxicity and could more effectively enter cancer cells with FR over-expression. The QDs with 4-5 nm in diameter were relatively easy to enter the cell and to be removed through kidneys, so it is more suitable for biomedical applications for bioprobes and bioimaging.


Assuntos
Compostos de Cádmio , Receptor 1 de Folato/química , Ácido Fólico/química , Pontos Quânticos , Compostos de Selênio , Sulfetos , Compostos de Zinco , gama-Ciclodextrinas/química , Compostos de Cádmio/síntese química , Compostos de Cádmio/química , Compostos de Cádmio/metabolismo , Compostos de Cádmio/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Células HeLa , Células Hep G2 , Humanos , Espectroscopia de Ressonância Magnética , Microscopia Eletrônica de Transmissão , Imagem Molecular/métodos , Pontos Quânticos/química , Pontos Quânticos/metabolismo , Pontos Quânticos/toxicidade , Compostos de Selênio/síntese química , Compostos de Selênio/química , Compostos de Selênio/metabolismo , Compostos de Selênio/toxicidade , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Sulfetos/síntese química , Sulfetos/química , Sulfetos/metabolismo , Sulfetos/toxicidade , Compostos de Zinco/síntese química , Compostos de Zinco/química , Compostos de Zinco/metabolismo , Compostos de Zinco/toxicidade
6.
Yi Chuan ; 35(8): 1014-22, 2013 Aug.
Artigo em Zh | MEDLINE | ID: mdl-23956090

RESUMO

Transposons or transposable elements (TEs) are ubiquitous and most abundant DNA components in higher eukaryotes. Recent sequencing of the Brassica rapa and B. oleracea genomes revealed that the amplification of TEs is one of the main factors inducing the difference in genome size. However, the expressions of TEs and the TE effects on gene regulation and functions of these two Brassica diploid species were unclear. Here, we analyzed the RNA sequencing data of leaves, roots, and stems from B. rapa and B. oleracea. Our data showed that overall TEs in either genome expressed at very low levels, and the expression levels of different TE categories and families varied among different organs. Moreover, even for the same TE category or family, the expression activities were distinct between the two Brassica diploids. Forty-one and nine LTR retrotransposons with the transcripts that read into their adjacent sequences have the distances shorter than 2 kb and 100 bp compared to the downstream genes. These LTR retrotransposon readout transcriptions may produce sense or antisense transcripts of nearby genes, with the effects on activating or silencing corresponding genes. Meanwhile, intact LTRs were detected at stronger readout activities than solo LTRs. Of the TEs inserted into genes, the frequencies were ob-served at a higher level in B. rapa than in B. oleracea. In addition, DNA transposons were prone to insert or retain in the intronic regions of genes in either Brassica genomes. These results revealed that the TEs may have potential effects on regulating protein coding genes.


Assuntos
Genoma de Planta , Retroelementos , Brassica , Brassica rapa/genética , Elementos de DNA Transponíveis , Evolução Molecular , Regulação da Expressão Gênica , Sequências Repetidas Terminais
7.
Biomed Mater ; 18(2)2023 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-36720160

RESUMO

We developed a pH/glutathione (GSH) dual-responsive smart nano-drug delivery system to achieve targeted release of a chemotherapeutic drug at breast tumor site. Doxorubicin (DOX) was linked to polyethylene glycol (PEG) through cis-aconitic anhydride (CA) and disulfide bonds (SS) to obtain the PEG-SS-CA-DOX prodrug, which spontaneously assembled into nanomicelles with a particle size of 48 ± 0.45 nm. PEG-SS-CA-DOX micelles achieved an efficient and rapid release of DOX under dual stimulation by weak acidic pH and high GSH content of tumors, with the release amount reaching 88.0% within 48 h. Cellular uptake experiments demonstrated that PEG-SS-CA-DOX micelles could efficiently transport DOX into cells and rapidly release it in the tumor microenvironment. In addition,in vivoantitumor experiments showed that PEG-SS-CA-DOX had a high inhibition rate of 70% against 4T1 breast cancer cells along with good biosafety. In conclusion, dual-responsive smart nanomicelles can achieve tumor-targeted drug delivery and specific drug release, thus improving therapeutic efficacy of drugs.


Assuntos
Neoplasias da Mama , Micelas , Humanos , Feminino , Doxorrubicina/química , Polietilenoglicóis/química , Glutationa , Concentração de Íons de Hidrogênio , Portadores de Fármacos/química , Microambiente Tumoral
8.
Mar Environ Res ; 190: 106110, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37537017

RESUMO

Scleractinian cold-water corals (CWCs) are one of the most important habitat engineers of the deep sea. Although the South China Sea (SCS) abuts the biodiversity center of scleractinian CWCs in the western Pacific, only a few sporadic records are available. We discovered new CWC sites by means of trawl sampling and video observation along the continental shelf of the northwestern SCS. All trawled scleractinian CWC specimens were identified to species level according to skeleton morphology and structure. The living CWCs and associated fauna recorded in the video were -identified to a higher level of classification. Scleractinian corals were identified to genus level, while non-scleractinian CWCs were identified to family level and given general names such as gorgonian corals, bamboo corals and black corals. Associated benthic dwellers were divided into major categories. A total of 28 scleractinian CWC species were identified to 7 families, 15 genera, and 1 additional subgenus. Among them, 13 species were colonial, including important habitat-forming species in the genera Eguchipsammia, Dendrophyllia and Cladopsammia. Non-scleractinian CWCs were identified to 7 families, including 4 families gorgonian corals, 1 family bamboo corals, and 2 families black corals. Gorgonian corals were the most abundant non-scleractinian CWCs in this region. Meanwhile, starfish, sea anemones, fish, gastropods, echinoderms, and other associated benthic fauna were recorded in the CWC habitats, with starfish belonging to the order Brisingida being most common. New scleractinian CWC assemblages were discovered along the continental seabed mounds in the northwestern SCS. This study highlights the remarkable diversity of cold-water scleractinian corals in the whole SCS, and shows the potential widespread distribution and conservation prospect of CWC habitats in this region.


Assuntos
Antozoários , Animais , Ecossistema , Água , Biodiversidade , China
9.
Chemistry ; 18(6): 1650-8, 2012 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-22213427

RESUMO

The use of active components from important medical herbs has proved effective in treating various cancers. Glycyrrhizic acid (GA) is one of the many interesting triterpenoic acids with anticancerogenic potential, and is known to trigger apoptosis in hepatocarcinoma cells. In this study we combined quantum dots (QDs) with GA in the presence of ß-cyclodextrin (ß-CD), and prepared ß-CD/GA-functionalised QDs, which led to improved antitumor activity and induced apoptosis in hepatocarcinoma cells. These compounds showed a better selectivity for hepatic cells compared to HeLa and ECV-304 cells. Hoechst and annexin V-FITC staining and mitochondrial membrane potential (MMP) experiments proved an apoptotic effect of these compounds on HepG2 cells. At the same time, transmission electron microscopy (TEM) showed obvious features of apoptosis, for example, irregularities of nuclear shapes, mitochondria swelling, clumping and peripheral chromatin condensation, zeiosis or blebbing of the plasma membrane and formation of apoptotic bodies. It is notable that ß-CD/GA-functionalised QDs showed effective cell growth inhibition by triggering G0/G1 phase arrest and inducing apoptosis through an reactive oxygen species mediated mitochondrial dysfunction pathway. ß-CD/GA-functionalised QDs primarily induced apoptotic response in a time- and dose-dependent manner, but little apoptosis appeared with L-Cys-ß-CD-functionalised QDs or GA alone. These studies suggest that ß-CD/GA-functionalised QDs have therapeutic potential against cancer.


Assuntos
Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/metabolismo , Ácido Glicirrízico/metabolismo , Pontos Quânticos , beta-Ciclodextrinas/química , Relação Dose-Resposta a Droga , Fase G1/efeitos dos fármacos , Ácido Glicirrízico/química , Ácido Glicirrízico/uso terapêutico , Células HeLa , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fase de Repouso do Ciclo Celular/efeitos dos fármacos , beta-Ciclodextrinas/metabolismo , beta-Ciclodextrinas/uso terapêutico
10.
Exploration (Beijing) ; 2(4): 20220082, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37325608

RESUMO

InP quantum dots (QDs) are a promising and environment-friendly alternative to Cd-based QDs for in vitro diagnostics and bioimaging applications. However, their poor fluorescence and stability severely limit their biological applications. Herein, we synthesize bright (∼100%) and stable InP-based core/shell QDs by using cost-effective and low-toxic phosphorus source, and then aqueous InP QDs are prepared with quantum yield over 80% by shell engineering. The immunoassay of alpha-fetoprotein can be detected in the widest analytical range of 1-1000 ng ml-1 and the limit of detection of 0.58 ng ml-1 by using those InP QDs-based fluorescent probes, making it the best-performing heavy metal-free detection reported so far, comparable to state-of-the-art Cd-QDs-based probes. Furthermore, the high-quality aqueous InP QDs exhibit excellent performance in specific labeling of liver cancer cells and in vivo tumor-targeted imaging of live mice. Overall, the present work demonstrates the great potential of novel high-quality Cd-free InP QDs in cancer diagnosis and image-guided surgery.

11.
ACS Nano ; 16(1): 1421-1435, 2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-34962119

RESUMO

Combinatorial cancer therapies based on nanomedicine have emerged as a promising strategy to achieve potentiated treatment efficiency. Herein, cisplatin (CDDP) prodrug (Pt-CD) and a mitochondria-targeted near-infrared (NIR) photosensitizer IR780 were combined to construct a multifunctional nanomedicine IR780@Pt NPs through a supramolecular self-assembly strategy. Targeted mitochondrial dysfunction of cancer cells was sufficiently induced under NIR laser irradiation through both photothermal and photodynamic effects, inhibiting the overactive mitochondrial energy pathways of cancer cells. The mitochondrial dysfunction significantly attenuated the crosstalk between mitochondria and nucleus via the cellular ATP energy chain, leading to obvious down-regulation of the key proteins of the nucleotide excision repair (NER) pathway. Thereby, the chemotherapeutic effect of CDDP could be significantly potentiated because of reduced DNA lesion repair capacity by ERCC1-XPF nuclease system. Moreover, IR780@Pt NPs exhibited excellent NIR fluorescence and photoacoustic (PA) imaging capacity for in vivo imaging-guided NIR laser treatment. Ultimately, the IR780@Pt NPs mediated combinatorial chemophototherapy achieved potentiated anticancer efficacy against cancer cells in vitro and tumor inhibition performance in vivo. Overall, this study highlighted the significance of nanomedicine mediated targeted induction of mitochondrial dysfunction to potentiate chemotherapy for efficient combinatorial cancer therapy.


Assuntos
Nanopartículas , Fotoquimioterapia , Cisplatino/farmacologia , Fotoquimioterapia/métodos , Nanomedicina , Raios Infravermelhos , Nanopartículas/uso terapêutico , Nanomedicina Teranóstica/métodos , Mitocôndrias , Fototerapia/métodos , Linhagem Celular Tumoral
12.
Chemistry ; 17(18): 5171-9, 2011 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-21465588

RESUMO

Quantum dots (QDs) have the potential to serve as photostable beacons to track siRNA delivery, which is fast becoming an attractive approach to probe gene function in cells. In this paper, we synthesized QD nanoparticles coated with ß-cyclodextrin (ß-CD) coupled to amino acids with different surface charges (positive, negative, and neutral) through direct ligand-exchange reactions and used them to deliver siRNA. We found that these QDs are diffluent in biological buffer with high colloidal stability and have strong optical emission properties similar to those of tri-n-octylphosphine oxide (TOPO)-coated QDs and also have a long fluorescence lifetime (12.5 ns for L-His-ß-CD-coated CdSe/ZnSe QDs). The results of in vitro cytotoxicity and internalization of these modified QDs in normal and cancer cells showed that the ß-CD coupled to amino acid outlayers greatly improved the biocompatibility of QDs, and conferred with lower cytotoxicity even at very high concentration. In particular, the L-His-ß-CD-coated CdSe/ZnSe QDs presented lower cytotoxicity to these cells (CC(50) value is 180.6±3.4 µg mL(-1) in ECV-304 cells for 48 h). Transmission electron microscope (TEM) images showed that the QDs were localized in vesicles in the cytoplasm of the cells. Furthermore, compared with existing transfection agents, gene-silencing efficiency of the modified QDs was slightly improved for HPV18 E6 gene in HeLa cells by gel electrophoresis analysis. Finally, the unique optical properties of QDs allow visible imaging of siRNA delivery in live cells. Taken together, our study not only provides new insights into the mechanisms of amino acid mediated delivery, but also greatly facilities the monitoring of gene-silencing studies.


Assuntos
Aminoácidos/química , Pontos Quânticos , RNA Interferente Pequeno/metabolismo , beta-Ciclodextrinas/síntese química , Linhagem Celular Tumoral , Proteínas de Ligação a DNA , Inativação Gênica , Células HeLa , Papillomavirus Humano 18/genética , Humanos , Nanopartículas/química , Nanopartículas/ultraestrutura , Proteínas Oncogênicas Virais/análise , RNA Interferente Pequeno/análise , Espectrometria de Fluorescência , beta-Ciclodextrinas/química
13.
Int J Nanomedicine ; 16: 7023-7033, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34703225

RESUMO

PURPOSE: Gold nanoparticles (AuNPs) with good physical and biological properties are often used in medicine, diagnostics, food, and similar industries. This paper explored an AuNPs drug delivery system that had good target selectivity for folate-receptor overexpressing cells to induce apoptosis. METHODS: A novel drug delivery system, Au@MPA-PEG-FA-PTX, was developed carrying paclitaxel (PTX) on folic acid (FA) and polyethylene glycol (PEG)-modified AuNPs. The nanomaterial was characterized by transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), and ultraviolet-visible spectroscopy (UV-Vis). Also, the biological activity of the AuNPs drug delivery system was examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in HL-7702, Hela, SMMC-7721, and HCT-116 cells. Furthermore, apoptotic activity using annexin V-FITC, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) levels was estimated by flow cytometry and fluorescence microscopy. RESULTS: Au@MPA-PEG-FA-PTX exhibited a distinct core-shell structure with a controllable size of 28±1 nm. Also, the AuNPs maintained good dispersion and spherical shape uniformity before and after modification. The MTT assay revealed good antitumor activity of the Au@MPA-PEG-FA-PTX against the Hela, SMMC-7721, and HCT-116 cells, while Au@MPA-PEG-FA-PTX produced better pharmacological effects than PTX in isolation. Further mechanistic investigation revealed that effective internalization of AuNPs by folate-receptor overexpressing cancer cells induced cell apoptosis through excessive production of intracellular ROS. CONCLUSION: The AuNPs drug delivery system showed good target selectivity for folate-receptor overexpressing cancer cells to induce target cell-specific apoptosis. These AuNPs may have great potential as theranostic agents such as in cancer.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Linhagem Celular Tumoral , Portadores de Fármacos , Ácido Fólico , Ouro , Paclitaxel/farmacologia , Polietilenoglicóis
14.
Pharmaceuticals (Basel) ; 14(2)2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33525717

RESUMO

Functionalized gold nanoparticles (AuNPs) have been successfully used in many fields as a result of having low cytotoxicity, good biocompatibility, excellent optical properties, and their ability to target cancer cells. Here, we synthesized AuNP carriers that were modified by hyaluronic acid (HA), polyethylene glycol (PEG), and adipic dihydrazide (ADH). The antitumor drug doxorubicin (Dox) was loaded into AuNP carriers and attached chemically. The Au nanocomposite AuNPs@MPA-PEG-HA-ADH-Dox was able to disperse uniformly in aqueous solution, with a diameter of 15 nm. The results of a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay indicated that AuNP carriers displayed very little toxicity toward cells in high doses, although the antitumor properties of Au nanocomposites were significantly enhanced. Cellular uptake experiments demonstrated that AuNPs modified with hyaluronic acid were more readily ingested by HepG2 and HCT-116 cells, as they have a large number of CD44 receptors. A series of experiments measuring apoptosis such as Rh123 and annexin V-FITC staining, and analysis of mitochondrial membrane potential (MMP) analysis, indicated that apoptosis played a role in the inhibition of cell proliferation by AuNPs@MPA-PEG-HA-ADH-Dox. Excessive production of reactive oxygen species (ROS) was the principal mechanism by which the Au nanocomposites inhibited cell proliferation, leading to apoptosis. Thus, the Au nanocomposites, which allowed cell imaging in real-time and induced apoptosis in specific cell types, represent theragnostic agents with potential for future clinical applications in bowel cancer.

15.
Int J Nanomedicine ; 15: 2765-2776, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32425520

RESUMO

PURPOSE: Over the past decades, quantum dots (QDs) have shown the broad application in diverse fields, especially in intracellular probing and drug delivery, due to their high fluorescence intensity, long fluorescence lifetime, strong light-resistant bleaching ability, and strong light stability. Therefore, we explore a kind of therapeutic potential against cancer with fluorescent imaging. METHODS: In the current study, a new type of QDs (QDs@L-Cys-TAEA-5-FUA) capped with L-cysteine (L-Cys) and tris(2-aminoethyl)amine (TAEA) ligands, and conjugated with 5-fluorouracil-1-acetic acid (5-FUA) has been synthesized. Ligands were characterized by electrospray ionization mass spectrometry and H-nuclear magnetic resonance (1H NMR) spectroscopy. The modified QDs were characterized by transmission electron microscopy, ultraviolet and visible spectrophotometry (UV-Vis), and fluorescence microscopy. And the biological activity of modified QDs was explored by using MTT assay with HeLa, SMMC-7721 HepG2, and QSG-7701 cells. The fluorescence imaging of modified QDs was obtained by fluorescence microscope. RESULTS: The modified QDs are of controllable sizes in the range of 4-5 nm and they possess strong optical emission properties. UV-Vis and fluorescence spectra demonstrated that the L-Cys-TAEA-5-FUA was successfully incorporated into QD nanoparticles. The MTT results demonstrated that L-Cys-TAEA-5-FUA modified QDs could efficiently inhibit the proliferation of cancer cells as compared to the normal cells, illustrating their antitumor efficacy. The mechanistic studies revealed that the effective internalization of modified QDs inside cancer cells could inhibit their proliferation, through excessive production of intracellular reactive oxygen species, leading to apoptosis process. CONCLUSION: The present study suggests that modified QDs can enter cells efficiently and could be employed as therapeutic agents for the treatment of various types of cancers with fluorescent imaging.


Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Fluoruracila/farmacologia , Pontos Quânticos/química , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Cisteína/química , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Etilenodiaminas/química , Fluoruracila/administração & dosagem , Fluoruracila/química , Células HeLa , Células Hep G2 , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Microscopia Eletrônica de Transmissão , Microscopia de Fluorescência , Pontos Quânticos/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Espectrofotometria Ultravioleta
16.
Int J Nanomedicine ; 15: 1611-1622, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32210555

RESUMO

PURPOSE: Quantum dots (QDs) are used as fluorescent probes due to their high fluorescence intensity, longevity of fluorescence, strong light-resistant bleaching ability and high light stability. Therefore, we explore a more precise probe that can target an organelle. METHODS: In the current study, a new class of fluorescence probes were developed using QDs capped with 4 different L-cysteine-polyamine-morpholine linked by mercapto groups. Ligands were characterised by Electrospray ionization mass spectrometry (ESI-MS), H-Nuclear Magnetic Resonance (1H NMR) spectroscopy, and 13C NMR spectroscopy. Modified QDs were characterized by Transmission Electron Microscope (TEM), Ultraviolet and visible spectrophotometry (UV-Vis), and fluorescence microscopy. And the biological activity of modified QDs was explored by using MTT assay with HeLa, SMMC-7721 and HepG2 cells. The fluorescence imaging of modified QDs was obtained by confocal laser scanning fluorescence microscopy (CLSM). RESULTS: Synthesized QDs ranged between 4 to 5 nm and had strong optical emission properties. UV-Vis and fluorescence spectra demonstrated that the cysteine-polyamine-morpholine were successfully incorporated into QD nanoparticles. The MTT results demonstrated that modified QDs had lesser cytotoxicity when compared to unmodified QDs. In addition, modified QDs had strong fluorescence intensity in HeLa cells and targeted lysosomes of HeLa cells. CONCLUSION: This study demonstrates the modified QDs efficiently entered cells and could be used as a potential lysosome-targeting fluorescent probe.


Assuntos
Corantes Fluorescentes/química , Lisossomos/efeitos dos fármacos , Microscopia Confocal/métodos , Pontos Quânticos/química , Cisteína/química , Corantes Fluorescentes/análise , Células HeLa , Células Hep G2 , Humanos , Microscopia de Fluorescência , Morfolinas/química , Nanopartículas/química , Poliaminas/química , Pontos Quânticos/análise , Solubilidade , Espectrofotometria Ultravioleta
17.
Guang Pu Xue Yu Guang Pu Fen Xi ; 29(1): 217-21, 2009 Jan.
Artigo em Zh | MEDLINE | ID: mdl-19385243

RESUMO

In the present paper laser light scattering method was used to investigate the particle size and size distribution of nanoparticles simultaneously in urines of lithogenic patients and healthy persons. This method is economic, rapid, accurate and easy to operate. The results showed that healthy urines are more stable than lithogenic urines. In urines of healthy human, the ultrafine crystals were well scattered and not aggregated with a smaller size. However, the ultrafine crystals in lithogenic urine have a broad size distribution, which increases the aggregation trend of nanocrystals. Based on the intensity-autocorrelation curve, the stability of urine samples of both healthy human and lithogenic patients was comparatively investigated. The relationship between the measurement results and the methods of handling sample was studied. The results show that a stable urine sample can be obtained by diluting the urine with a ratio of 20%, then centrifuging it at 4,000 round per minute for 15 minutes or filtrating it with 1.2 microm cellulose acetate filter. The results of laser light scattering method are consistent with that obtained by transmission electron microscopy (TEM). The reasons for the stability of urines are explained from the points of Van der Waals force, urine viscosity, pH value, ionic strength, surface charge and zeta potential of the ultrafine crystals, and so on. The results in this paper provide a new thought for preventing formation and recurrence of urinary stones.


Assuntos
Nanopartículas , Tamanho da Partícula , Espalhamento de Radiação , Urina/química , Humanos , Lasers , Luz
18.
Artigo em Inglês | MEDLINE | ID: mdl-30593994

RESUMO

By introducing the S-aryl substituents at the central carbon on heptamethine cyanine, we have developed a near-infrared fluorescent probe Cy.7-PT. The probe had the high selectivity for the colorimetric detection of Cys/Hcy with the color changing from light green to blue. Cys could be quantitatively detected and the detection limit is 0.39 µM. Cell imaging and spiked samples experiments prove that the probe Cy.7-PT is suitable for monitoring and visualizing Cys in vitro and living cells.


Assuntos
Colorimetria/métodos , Cisteína/análise , Corantes Fluorescentes/química , Homocisteína/análise , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Células HeLa , Humanos , Espectrometria de Fluorescência
19.
ACS Omega ; 4(18): 17850-17856, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31681893

RESUMO

The surface modification of nanoparticles (NPs) can enhance cellular and intracellular targeting. A new type of polyamine-modified gold NPs (AuNPs) are designed and synthesized, which can be selectively absorbed onto the cell membrane. AuNPs with an average diameter of 4.0 nm were prepared and modified with polyamine (R-4C) through amidation. In order to detect the distribution of NPs within cells by fluorescence imaging, AuNP@MPA-R-4C was functionalized with fluorescein isothiocyanate (FITC). The fluorescence-labled NPs AuNP@MPA-R-4C-FITC demonstrated minimal cytotoxicity in several cell lines. Both confocal laser scanning microscopy and transmission electron microscopy demonstrated that AuNP@MPA-R-4C-FITC was distributed on the cell membrane. Compared with the free organic dye, the modified AuNPs showed significantly increased accumulation on the cell membrane after treatment for only 10 min. These results suggested that AuNP@MPA-R-4C-FITC can be used as a bioprobe targeting the cell membrane for various biological applications.

20.
Nanoscale Res Lett ; 13(1): 304, 2018 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-30269179

RESUMO

Functionalized gold nanoparticles (AuNPs) have widely applied in many fields, due to their good biocompatibility, a long drug half-life, and their bioactivity is related to their size and the modified ligands on their surface. Here, we synthesized the AuNPs capped with ligands that possess polyethylene glycol (PEG) and lithocholic acid (LCA) linked by carboxyl groups (AuNP@MPA-PEG-LCA). Our cytotoxicity results indicated that AuNP@MPA-PEG-LCA have better cell selectivity; in other words, it could inhibit the growth of multiple liver cancer cells more effectively than other cancer cells and normal cells. Apoptosis plays a role in AuNP@MPA-PEG-LCA inhibition cell proliferation, which was convincingly proved by some apoptotic index experiments, such as nuclear staining, annexin V-FITC, mitochondrial membrane potential (MMP) analysis, and AO/EB staining experiments. The most potent AuNP@MPA-PEG-LCA were confirmed to efficiently induce apoptosis through a reactive oxygen species (ROS) mediating mitochondrial dysfunction. And AuNP@MPA-PEG-LCA could be more effective in promoting programmed cell death of liver cancer cells.

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