RESUMO
Recently, molybdenum sulfide (MoS2) has shown great application potential in tumor treatment because of its good photothermal properties. Unfortunately, most of the current molybdenum disulfide-based nanotherapeutic agents suffer from complex preparation processes, low photothermal conversion efficiencies, and poor structural/compositional regulation. To address these issues, in this paper, a facile "confined solvothermal" method is proposed to construct an MoS2-loaded porous silica nanosystem (designated as MoS2@P-hSiO2). The maximum photothermal efficiency of 79.5% of molybdenum-based materials reported in the literature at present was obtained due to the ultrasmall MoS2 nanoclusters and the rich porous channels. Furthermore, both in vitro and in vivo experiments showed that the cascade hybrid system (MoS2/GOD@P-hSiO2) after efficient loading of glucose oxidase (GOD) displayed a significant tumor-suppressive effect and good biosafety through the combined effects of photothermal and enzyme-mediated cascade catalytic therapy. Consequently, this hybrid porous network system combining the in situ solvothermal strategy of inorganic functional components and the efficient encapsulation of organic enzyme macromolecules can provide a new pathway to construct synergistic agents for the efficient and safe treatment of tumors.
Assuntos
Molibdênio , Neoplasias , Dissulfetos , Humanos , Molibdênio/uso terapêutico , Neoplasias/tratamento farmacológico , Fototerapia , Porosidade , Dióxido de SilícioRESUMO
Identification of novel chemotypes with antimalarial efficacy is imperative to combat the rise of Plasmodium species resistant to current antimalarial drugs. We have used a hybrid target-phenotype approach to identify and evaluate novel chemotypes for malaria. In our search for drug-like aspartic protease inhibitors in publicly available phenotypic antimalarial databases, we identified GNF-Pf-4691, a 4-aryl- N-benzylpyrrolidine-3-carboxamide, as having a structure reminiscent of known inhibitors of aspartic proteases. Extensive profiling of the two terminal aryl rings revealed a structure-activity relationship in which relatively few substituents are tolerated at the benzylic position, but the 3-aryl position tolerates a range of hydrophobic groups and some heterocycles. Out of this effort, we identified (+)-54b (CWHM-1008) as a lead compound. 54b has EC50 values of 46 and 21 nM against drug-sensitive Plasmodium falciparum 3D7 and drug-resistant Dd2 strains, respectively. Furthermore, 54b has a long half-life in mice (4.4 h) and is orally efficacious in a mouse model of malaria (qd; ED99 â¼ 30 mg/kg/day). Thus, the 4-aryl- N-benzylpyrrolidine-3-carboxamide chemotype is a promising novel chemotype for malaria drug discovery.
Assuntos
Antimaláricos/farmacologia , Pirrolidinas/farmacologia , Administração Oral , Animais , Antimaláricos/administração & dosagem , Antimaláricos/química , Disponibilidade Biológica , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Malária/tratamento farmacológico , Camundongos , Microssomos Hepáticos/efeitos dos fármacos , Pirrolidinas/administração & dosagem , Pirrolidinas/química , Relação Estrutura-AtividadeRESUMO
INTRODUCTION: In this work, we have developed a novel "confined-growth" strategy to synthesize PEGylated multiple gold nanorices-encapsulated dual-mesoporous silica nanospheres (designated as PEGylated MGNRs@DMSSs) containing both small mesopores (2.5 nm) in the shell and large mesopores (21.7 nm) in the core based on a well-established, seed-mediated growth method. The photothermal effect and CT imaging ability were also studied. METHODS: The nanoparticles were characterized by Fourier transform infrared (FT-IR) spectra, N2 absorption isotherms, Field-emission scanning electron microscopy (FE-SEM), Transmission electron microscopy (TEM), Inductively coupled plasma atomic emission spectroscopy (ICP-AES) and Confocal microscopy. RESULTS: The longitudinally-localized surface (LSPR) absorption properties of MGNRs@DMSSs can be easily tuned by altering the amount of HAuCl4 in the gold growth solution. Additionally, the resultant PEGylated MGNRs@DMSSs have monodispersed, spherical morphology and good colloidal stability in an aqueous solution. More importantly, when exposed to NIR irradiation, the PEGylated MGNRs@DMSSs exhibit both higher temperature increments and better photothermal effects than that of single PEGylated gold nanorods at nearly an equivalent LSPR absorption. In addition, as CT contrast agents, the PEGylated MGNRs@DMSSs display a better CT imaging performance, in comparison with single PEGylated gold nanorods at the same Au concentration. CONCLUSION: Taken together, results indicate the potential for MGNRs@DMSSs used in CT imaging-guided photothermal therapy. Such a simple "confined-growth" strategy within a porous matrix offers a promising platform to design and prepare novel metal(s) oxide@silica nanocomposites for use in further cancer bio-imaging and therapy.
Assuntos
Carcinoma Hepatocelular/terapia , Ouro/química , Neoplasias Hepáticas/terapia , Nanocompostos/administração & dosagem , Fototerapia , Dióxido de Silício/química , Tomografia Computadorizada por Raios X/métodos , Animais , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Proliferação de Células , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Nus , Nanocompostos/química , Células Tumorais CultivadasRESUMO
OBJECTIVE: To observe whether Xuefu Zhuyu Decoction (XZD) could induce the differentiation of mesenchymal stem cells (MSCs) into cardiac myoid cells, thus seeking for safe and effective inducers. METHODS: The serum pharmacological method was used to induce. XZD containing serum was prepared. MSCs were isolated and cultured. The serum cytotoxicity was detected by MTT. The third generation of favorably grown cells was selected in this experiment. Cells were divided into three groups, i.e., the vehicle control group, the XZD containing serum induced group, and the 5-azacytidine induced group. Expressions of Desmin and alpha-actin were detected by immunocytochemical staining method. RESULTS: Before induction protein expressions of Desmin and alpha-actin were negative, and few was weakly positive. There was no statistical difference in the weak positive expression rate among the 3 groups (P > 0.05). After induction protein expressions of Desmin and alpha-actin were negative, and few was weakly positive in the vehicle control group. Protein expressions of Desmin and alpha-actin were positive in the XZC containing serum induced group and the 5-azacytidine induced group. There was statistical difference in the positive expression rate when compared with the vehicle control group (P > 0.05). CONCLUSIONS: XZD played a role in in vitro inducing differentiation MSCs to cardiac myoid cells. It might participate in expressions of Desmin and alpha-actin.