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Biomaterials ; 229: 119576, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31704467


Dual-modal imaging guided photodynamic therapy (PDT) of multifunctional nanocomposites holds great promise for precision tumor theranostics. However, poor heterogeneous interfacial compatibility between functional components, low hydrophilicity and complicated preparation of nanocomposites remain major obstacles for further bioapplication. Herein, a facile central metal-derived co-assembly strategy is developed to effectively integrate gadolinium porphyrin (GdTPP) contrast agent and Zinc porphyrin (ZnTPP) photosensitizer into a homogeneous GdTPP/ZnTPP nanocomposites (GZNs). GZNs possesses the following advantages: (1) Greatly improved interfacial compatibility facilitated by incorporating two metalporphyrins with same group (phenyl-) and different central metal atoms (Zn and Gd) leading to higher yield (4.7-5 fold) than either monocomponent nanoparticles. (2) Poor dispersity of GdTPP nanoparticles is greatly improved after integrating with ZnTPP blocks. (3) The GZNs inherit excellent fluorescence imaging, high relaxation rate (8.18 mM-1 s-1) and singlet oxygen production from two raw metalporphyrins. After camouflaging with homotypic cancer cell membrane for immunologic escape, the HeLa membrane coated GZNs (mGZNs) show enhanced in vivo MR/FL imaging guided anti-tumor targeting efficiency of 80.6% for HeLa cells. Our new strategy using central metal-derived co-assembly of homogeneous building blocks greatly improves interfacial compatibility to achieve combined functions for visualized cancer theranostics.

Biomacromolecules ; 20(5): 2148-2158, 2019 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-30995832


Poly(amidoamine) dendrimer (PAMAM) is well-known for its high efficiency as a drug delivery vehicle. However, the intrinsic cytotoxicity and lack of a detectable signal to facilitate tracking have impeded its practical applications. Herein, we have developed a novel label-free fluorescent and biocompatible PAMAM derivative by simple surface modification of PAMAM using acetaldehyde. The modified PAMAM possessed a strong green fluorescence, which was generated by the C=N bonds of the resulting Schiff Bases via n-π* transition, while the intrinsic cytotoxicity of PAMAM was simultaneously ameliorated. Through further PEGylation, the fluorescent PAMAM demonstrated excellent intracellular tracking in human melanoma SKMEL28 cells. In addition, our PEGylated fluorescent PAMAM derivative achieved enhanced loading and delivery efficiency of the anticancer drug doxorubicin (DOX) compared to the original PAMAM. Importantly, the accelerated kinetics of DOX-encapsulated fluorescent PAMAM nanocomposites in an acidic environment facilitated intracellular drug release, which demonstrated comparable cytotoxicity to that of the free-form doxorubicin hydrochloride (DOX·HCl) against melanoma cells. Overall, our label free fluorescent PAMAM derivative offers a new opportunity of traceable and controlled delivery for DOX and other drugs of potential clinical importance.

Chem Commun (Camb) ; 54(29): 3609-3612, 2018 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-29570195


A superior biocompatible spherical nucleic acid (SNA) conjugate was fabricated by grafting siRNA onto the surface of a core composed of a spherical DNA nanostructure that we have termed a DNA nanoclew (DC). After uptake by cultured cancer cells, SNA nanoparticles release engrafted siRNAs by cleavage of the intracellular Dicer enzyme. Moreover, in vitro experiments reveal that such SNAs demonstrate potent gene knockdown at both mRNA and protein levels, while with negligible cytotoxicity.

DNA/química , Sistemas de Liberação de Medicamentos/métodos , Técnicas de Silenciamento de Genes/métodos , Nanopartículas/química , RNA Interferente Pequeno/administração & dosagem , Inativação Gênica , Células HeLa , Humanos , Nanopartículas/toxicidade , Hibridização de Ácido Nucleico , Tamanho da Partícula , RNA Interferente Pequeno/química , RNA Interferente Pequeno/metabolismo , RNA Interferente Pequeno/toxicidade , Ribonuclease III/química
J Mater Chem B ; 6(47): 7862-7870, 2018 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-32255031


Nanohybrids fabricated with upconversion nanoparticles (UCNPs) and gold nanoparticles (NPs) hold great promise for near-infrared photothermal therapy (NIR-PTT) and upconversion fluorescence imaging. However, the obstacles of poor solubility in water and finite hydrophilic modification method for UCNPs limit their application in biological fields. Herein, we report a novel UCNP@Al(OH)3/Au nanohybrid mediated by a highly hydrophilic and biocompatible Al(OH)3 layer to realize a synergistic targeted PTT and fluorescence imaging capability to U87MG tumor-bearing mice under NIR light irradiation. The modification with Al(OH)3 layers can improve the water solubility of UCNPs. And cytotoxicity assays and hemolysis assay showed that the modification with Al(OH)3 layers makes UCNPs have low cytotoxicity and good biocompatibility. In addition, the Al(OH)3 layers are thin enough to allow fluorescence resonance energy transfer (FRET) between UCNPs and gold NPs to occur, giving the NPs a good PTT effect for tumor-bearing mice. Meanwhile, as the pH-sensitive Al(OH)3 layers decompose in acidic tumor microenvironments with Au NPs detached from their surface, the FRET effect no longer occurred, subsequently leading to the fluorescence intensity of naked UCNPs being recovered for good imaging effects. The study suggests that Al(OH)3 mediation layer as a promising hydrophilic nanoplatform can potentially be used for the preparation of superior hydrophilic NPs and pH-stimulated drug release carriers for theranostic application in vivo.

World J Gastroenterol ; 19(45): 8211-8, 2013 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-24363511


Helicobacter pylori (H. pylori) is a common human pathogen responsible for various gastric diseases. This bacterium relies on the production of urease and hydrogenase to inhabit the acidic environment of the stomach. Nickel is an essential cofactor for urease and hydrogenase. H. pylori has to uptake sufficient nickel ions for the maturation of urease, and on the other way, to prevent the toxic effects of excessive nickel ions. Therefore, H. pylori has to strike a delicate balance between the import of nickel ions, its efficient intracellular storage, and delivery to nickel-dependent metalloenzymes when required. The assembly and maturation of the urease enzyme is a complex and timely ordered process, requiring various regulatory, uptake, chaperone and accessory proteins. In this review, we focus on several nickel trafficking proteins involved in urease maturation: NikR, NixA, HypAB, UreEFGH, HspA, Hpn and Hpnl. The work will deepen our understanding of how this pathogenic bacterium adapts to severe habitant environments in the host.

Proteínas de Bactérias/metabolismo , Infecções por Helicobacter/microbiologia , Helicobacter pylori/enzimologia , Metaloproteínas/metabolismo , Níquel/metabolismo , Estômago/microbiologia , Urease/metabolismo , Animais , Proteínas de Bactérias/química , Transporte Biológico , Helicobacter pylori/patogenicidade , Humanos , Concentração de Íons de Hidrogênio , Metaloproteínas/química , Modelos Moleculares , Chaperonas Moleculares , Conformação Proteica , Proteínas Repressoras/metabolismo , Urease/química
Metallomics ; 5(7): 888-95, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23765120


Helicobacter pylori is a common human pathogen responsible for various gastric diseases. Bismuth can effectively inhibit the growth of this bacterium and is commonly recommended for the treatment of the related diseases. Translation elongation factors EF-Tu and EF-Ts are two important components of the protein translation system. EF-Ts has inhibitory effects on the GTPase activity of EF-Tu and enhances GDP release, a hint that careful timing for the introduction of EF-Ts in the elongation should be accomplished to prevent the complete inhibition of the elongation process. Bismuth inhibits the chaperone activity of EF-Tu, and has opposite effects on the elongation activity: inhibitory effects on the intrinsic GTPase activity and stimulation of GDP release. The present work deepens our understanding of the bacterial elongation process as mediated by EF-Tu and EF-Ts and extends our knowledge about the inhibitory effects of bismuth-based drugs against Helicobacter pylori.

Bismuto/farmacologia , Helicobacter pylori/efeitos dos fármacos , Fator Tu de Elongação de Peptídeos/metabolismo , Fatores de Alongamento de Peptídeos/metabolismo , Sequência de Bases , Primers do DNA , GTP Fosfo-Hidrolases/metabolismo , Helicobacter pylori/enzimologia , Helicobacter pylori/metabolismo