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1.
Front Oncol ; 14: 1366554, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38756665

RESUMO

Spontaneous splenic rupture is an extremely rare occurrence, often attributed to tumorous pathologies. Among these, primary splenic angiosarcoma stands as a malignancy arising from the endothelial cells within the spleen. While sporadic cases have been reported globally, there remains a lack of comprehensive consensus on standardized approaches for diagnosis and treatment. We report a case of an 83-year-old male who underwent emergency enhanced CT due to sudden shock, revealing significant intra-abdominal fluid accumulation. Emergency surgery revealed splenic rupture necessitating splenectomy. Histopathological examination confirmed the diagnosis of splenic angiosarcoma. Despite successful surgery, the patient succumbed to severe complications two weeks postoperatively.

2.
Nurs Open ; 10(7): 4526-4535, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36855236

RESUMO

AIM: To evaluate the effect of enhanced recovery after surgery (ERAS)-optimized management system with nurse-led multidisciplinary cooperation. DESIGN: A quasi-experimental design. METHODS: Nursing department cooperated with medical and clinical department to establish an ERAS-optimized management system. After the system was developed, it was applied in surgical departments of the hospital. Using convenience sampling, 220 selective surgical patients, 82 nurses and 98 doctors from January 1st, 2021 to July 31st, 2021 were selected as the trial group. 220 selective surgical patients, 82 nurses and 98 doctors were selected as the control group from January 1st, 2020 to July 31st, 2020. ERAS observation indicators were compared between the two groups before and 6 months after implementation. The nurse professional identity scores and satisfaction of medical cooperation scores of the two groups at different time points were analysed by repeated analysis of variance. RESULTS: After the implementation, ERAS observation indicators in the trial group were better than the control group (p < 0.05). There were significant differences in the group main effect, time main effect and interaction effect of nurse professional identity scores, satisfaction of medical cooperation scores and scores in all dimensions between the two groups (p < 0.05). The scores of the experimental group at 3 months and 6 months after implementation were better than those of the control group (p < 0.05). CONCLUSIONS: Enhanced recovery after surgery-optimized management system with nurse-led multidisciplinary cooperation was an effective working method. It could promote patients recovery and enhance nurse professional identity.


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Humanos , Papel do Profissional de Enfermagem , Tempo de Internação
3.
Se Pu ; 41(3): 281-286, 2023 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-36861212

RESUMO

Two-dimensional liquid chromatography (2D-LC) has gained increased attention because of its high peak capacity for separating complex samples. However, preparative 2D-LC aimed at isolating compounds is significantly different compared with one-dimensional liquid chromatography (1D-LC) in terms of method development and system configuration; thus, it is less developed than its analytical counterpart. The use of 2D-LC in large-scale product preparation has rarely been reported. Hence, a preparative 2D-LC system was developed in this study. The system was composed of one set of preparative LC modules as a separation system, with a dilution pump, switch valves, and trap column array as the interface, to enable the simultaneous isolation of several compounds. Tobacco was used as a sample, and the developed system was applied to isolate nicotine, chlorogenic acid, rutin, and solanesol. The chromatographic conditions were developed by investigating the trapping efficiency of different types of trap column packings, and chromatographic behaviors under different overload conditions. The four compounds were isolated in one 2D-LC run with high purity. The developed system features low cost because it employs medium-pressure isolation, excellent automation owing to its use of an online column switch, high stability, and capability for large-scale production. The isolation of chemicals from tobacco leaves as pharmaceutical raw materials could aid in the development of the tobacco industry and promote the local agricultural economy.


Assuntos
Ácido Clorogênico , Nicotiana , Cromatografia Líquida , Nicotina , Folhas de Planta
4.
Connect Tissue Res ; 64(1): 26-39, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35723580

RESUMO

PURPOSE: The two structural components contributing to joint contracture formation are myogenic and arthrogenic contracture, and myofibrosis is an important part of myogenic contracture. Myofibrosis is a response to long-time immobilization and is described as a condition with excessive deposition of endomysial and perimysial connective tissue components in skeletal muscle. The purpose of this study was to confirm whether metformin can attenuate the formation of myogenic contracture and myofibrosis through the phosphorylation level of adenosine monophosphate-activated protein kinase (AMPK) and inhabitation of subsequent transforming growth factor beta (TGF-ß) 1/Smad signaling pathway. MATERIALS AND METHODS: An immobilized rat model was used to determine whether metformin could inhibit myogenic contracture and myofibrosis. The contents of myogenic contracture of knee joint was calculated by measuring instrument of range of motion (ROM), and myofibrosis of rectus femoris were determined by ultrasound shear wave elastography and Masson staining. Protein expression of AMPK and subsequent TGF-ß1/Smad signaling pathway were determined by western blot. Subsequently, Compound C, a specific AMPK inhibitor, was used to further clarify the role of the AMPK-mediated inhibition of TGF-ß1/Smad signaling pathway. RESULTS: We revealed that the levels of myogenic contracture and myofibrosis were gradually increased during immobilization, and overexpression of TGF-ß1-induced formation of myofibrosis by activating Smad2/3 phosphorylation. Activation of AMPK by metformin suppressed overexpression of TGF-ß1 and TGF-ß1-induced Smad2/3 phosphorylation, further reducing myogenic contracture and myofibrosis during immobilization. In contrast, inhibition of AMPK by Compound C partially counteracted the inhibitory effect of TGF-ß1/Smad signaling pathway by metformin. CONCLUSION: Notably, we first illustrated the therapeutic effect of metformin through AMPK-mediated inhibition of TGF-ß1/Smad signaling pathway in myofibrosis, which may provide a new therapeutic strategy for myogenic contracture.


Assuntos
Contratura , Metformina , Ratos , Animais , Metformina/farmacologia , Fator de Crescimento Transformador beta1/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Quinases Ativadas por AMP/farmacologia , Contratura/metabolismo , Transdução de Sinais , Articulação do Joelho/metabolismo , Proteínas Smad/metabolismo
5.
Cancers (Basel) ; 14(22)2022 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-36428785

RESUMO

Extracellular vesicles (EVs) are heterogeneous membrane-encapsulated vesicles released by most cells. They act as multifunctional regulators of intercellular communication by delivering bioactive molecules, including non-coding RNAs (ncRNAs). Metastasis is a major cause of cancer-related death. Most cancer cells disseminate and colonize a specific target organ via EVs, a process known as "organ-specific metastasis". Mounting evidence has shown that EVs are enriched with ncRNAs, and various EV-ncRNAs derived from tumor cells influence organ-specific metastasis via different mechanisms. Due to the tissue-specific expression of EV-ncRNAs, they could be used as potential biomarkers and therapeutic targets for the treatment of tumor metastasis in various types of cancer. In this review, we have discussed the underlying mechanisms of EV-delivered ncRNAs in the most common organ-specific metastases of liver, bone, lung, brain, and lymph nodes. Moreover, we summarize the potential clinical applications of EV-ncRNAs in organ-specific metastasis to fill the gap between benches and bedsides.

6.
Cartilage ; 13(1): 19476035221074024, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35255737

RESUMO

OBJECTIVE: We evaluated the ability of miR-379-5p to influence the proliferation of osteoarthritis chondrocytes and elucidated the regulatory mechanism of miR-379-5p in osteoarthritis. METHODS: Real time polymerase chain reaction (RT- PCR) was used to detect the expression of miR-379-5p and YBX1 in knee articular cartilages of human. Cell proliferation, inflammatory factors, extracellular matrix (ECM) degradation-associated proteins and proteins in PI3K/Akt pathway were assessed in rat primary chondrocytes treated with interleukin (IL)-1ß or/and miR-379-5p mimics or miR-379-5p inhibitor via cell counting assay kit-8 (CCK-8), enzyme-linked immunosorbent assay (ELISA), immunofluorescence and Western blotting (WB). The target of miR-379-5p predicted by TargetScan and miRwalk software was verified by luciferase reporter assay. Safranin O-fast green staining, immunohistochemistry, and WB were performed to observe the effect of miR-379-5p agomir on development of osteoarthritis in rats. RESULTS: MiR-379-5p was down-regulated in human osteoarthritic tissues and negatively correlated with YBX1 expression. High level of miR-379-5p in chondrocytes with IL-1ß stimulated increased cell viability, the expression of proliferation-related protein and extracellular matrix (ECM)-related proteins collagen II and aggrecan. However, the expression of inflammatory factors and ECM-related proteins matrix metalloproteinases (MMP-1) and MMP-13 was decreased. Luciferase reporting assay verified the targeting relationship between miR-379-5p and YBX1. This function of miR-379-5p was exerted through PI3K/Akt pathway and could be blocked by the PI3K/Akt pathway inhibitor LY294002. MiR-379-5p agomir promoted the articular chondrocytes proliferation and alleviated cartilage degradation in vivo. CONCLUSION: Our findings reveal that miR-379-5p can promote the articular chondrocytes proliferation in osteoarthritis (OA) by interacting with YBX1 and regulating PI3K/Akt pathway. Restoring miR-379-5p might be a future therapeutic strategy for OA.


Assuntos
Cartilagem Articular , Proteínas de Ligação a DNA , MicroRNAs , Osteoartrite , Animais , Apoptose , Cartilagem Articular/metabolismo , Proliferação de Células , Condrócitos/metabolismo , Proteínas de Ligação a DNA/metabolismo , MicroRNAs/genética , Osteoartrite/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos
7.
Adv Sci (Weinh) ; 8(14): e2100165, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34145978

RESUMO

Design of new nanoplatforms that integrates multiple imaging and therapeutic components for precision cancer nanomedicine remains to be challenging. Here, a facile strategy is reported to prepare polydopamine (PDA)-coated molybdenum disulfide (MoS2 ) nanoflakes as a nanocarrier to load dual drug cisplatin (Pt) and 1-methyl-tryptophan (1-MT) for precision tumor theranostics. Preformed MoS2 nanoflakes are coated with PDA, modified with methoxy-polyethylene glycol (PEG)-amine, and loaded with 1-MT and Pt. The formed functional 1-MT-Pt-PPDA@MoS2 (the second P stands for PEG) complexes exhibit good colloidal stability and photothermal conversion efficiency (47.9%), dual pH-, and photothermal-sensitive drug release profile, and multimodal thermal, computed tomography and photoacoustic imaging capability. Due to the respective components of Pt, MoS2 , and 1-MT that can block the immune checkpoint associated to tumoral indoleamine 2,3-dioxygenase-induced tryptophan metabolism, tri-mode chemo-photothermo-immunotherapy of tumors can be realized. In particular, under the near infrared laser irradiation, fast release of both drugs can be facilitated to achieve cooperative tumor therapy effect, and the combined immunogenic cell death induced by the dual-mode chemo-photothermo treatment and the 1-MT-induced immune checkpoint blockade can boost enhanced antitumor immune response to generate significant cytotoxic T cells for tumor killing. The developed 1-MT-Pt-PPDA@MoS2 complexes may be used as an intelligent nanoplatform for cooperative precision imaging-guided combinational tumor therapy.


Assuntos
Antineoplásicos/administração & dosagem , Dissulfetos/administração & dosagem , Imunoterapia/métodos , Molibdênio/administração & dosagem , Neoplasias/terapia , Fototerapia/métodos , Radiografia Intervencionista/métodos , Animais , Linhagem Celular Tumoral , Terapia Combinada , Modelos Animais de Doenças , Camundongos , Sistemas de Liberação de Fármacos por Nanopartículas , Técnicas Fotoacústicas , Tomografia Computadorizada por Raios X
8.
Heliyon ; 7(3): e06427, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33748486

RESUMO

The fruit fly Drosophila suzukii is a fruit crop pest that causes a severe economic threat to soft summer fruit worldwide. The male sex pheromone, cis-vaccenyl acetate (cVA) has multiple functions in intra-species communication in Drosophila melanogaster, which is required in male to suppress male-male courtship. D. suzukii males do not produce cVA; however, the odorant receptor for cVA (Or67d) is still functional. The lack of cVA in D. suzukii casts the question of whether this pheromone might have been replaced by another compound similar to cVA that disrupts mating in D. suzukii. In order to address this question, we cloned two D. suzukii adult antenna-specific odorant-binding proteins (OBPs) DsOBP69a and DsOBP76a and aligned with their D. melanogaster orthologues. Moreover, we examined the binding properties of the newly identified recombinant proteins against 26 potential ligands including cVA, using the fluorescence-based ligand binding assay. The alignment showed that DsOBP69a and DsOBP76a, have six conserved cysteines and belong to the classic OBP family. Furthermore, our results revealed that cVA did not bind to DsOBP69a or DsOBP76a proteins. Interestingly, the floral odorant ß-ionone and the bitter substance berberine chloride and coumarin displayed high binding ability. It is also worth noting that DsOBP69a and DsOBP76a have different affinities to (Z)-7-Tricosene that may reflect different functional roles. These findings suggest that DsOBP69a and DsOBP76a are potentially involved in olfaction and gustation of D. suzukii.

10.
ACS Appl Mater Interfaces ; 13(5): 6069-6080, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33501834

RESUMO

The development of functional intelligent theranostic nanoplatform for imaging-directed synchronous inhibition of primary tumor and tumor metastasis is still a challenging task. We present here the creation of functional dendrimer-entrapped CuS nanoparticles (CuS DENPs) complexed with plasmid DNA-encoding hypermethylation in cancer 1 (pDNA-HIC1) for photoacoustic (PA) imaging-directed simultaneous inhibition of tumors and tumor metastasis. Poly(amidoamine) dendrimers of generation 5 were covalently attached with 1,3-propane sultone and arginine-glycine-aspartic acid (RGD) peptide through a spacer of poly(ethylene glycol) and adopted for the templated synthesis of CuS NPs. The prepared functional RGD-CuS DENPs possess a mean CuS core diameter of 4.2 nm, good colloidal stability, and an excellent absorption feature in the second near-infrared window, thus having a photothermal conversion efficiency of 49.8% and an outstanding PA imaging capability. The functional DENPs can effectively deliver pDNA-HIC1 to prevent cancer cell invasion and metastasis in a serum-enhancing manner by virtue of zwitterionic modification-rendered antifouling property. The developed RGD-CuS DENPs/pDNA polyplexes display αvß3 integrin-targeted enhanced anticancer activity through the combined CuS NP-mediated photothermal therapy (PTT) and pDNA delivery-rendered cancer cell metastasis inhibition. This can also be proven by the therapeutic efficacy of a triple-negative breast cancer model in vivo, where inhibition of both the primary subcutaneous tumor and lung metastasis can be realized. The created dendrimer-CuS hybrid nanoplatform represents one of the updated designs of nanomedicine for PA imaging-directed combination PTT/gene therapy of tumors and tumor metastasis.


Assuntos
Antineoplásicos/farmacologia , Incrustação Biológica/prevenção & controle , Neoplasias da Mama/tratamento farmacológico , Cobre/farmacologia , Dendrímeros/farmacologia , Nanopartículas/química , Técnicas Fotoacústicas , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Neoplasias da Mama/diagnóstico por imagem , Cobre/química , Dendrímeros/química , Feminino , Humanos , Neoplasias Mamárias Experimentais/diagnóstico por imagem , Neoplasias Mamárias Experimentais/tratamento farmacológico , Camundongos , Oligopeptídeos/química , Oligopeptídeos/farmacologia , Tamanho da Partícula , Fototerapia , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Propriedades de Superfície , Células Tumorais Cultivadas
11.
Artigo em Inglês | MEDLINE | ID: mdl-35003311

RESUMO

BACKGROUND: Alcoholic fatty liver disease (AFLD) is the first stage of the alcoholic liver disease course. Yin-Chen-Hao-Tang (YCHT) has a good clinical effect on the treatment of AFLD, but its molecular mechanism has not been elucidated. In this study, we tried to explore the molecular mechanism of YCHT in improving hepatocyte steatosis in AFLD mice through network pharmacology and RNA sequencing (RNA-Seq) transcriptomics. METHODS: Network pharmacological methods were used to analyze the potential therapeutic signaling pathways and targets of YCHT on AFLD. Then, the AFLD mice model was induced and YCHT was administered concurrently. Liver injury was measured by serum alanine aminotransferase (ALT) activity and liver tissue H&E staining, and liver steatosis was determined by serum triglyceride (TG) level and liver tissue Oil Red staining. The molecular mechanism of YCHT on prevention and treatment of mice AFLD was investigated according to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the differential expression genes data obtained by liver tissue RNA-Seq. Finally, ethanol-induced AFLD AML12 hepatocyte model was established, YCHT with or without PPARα agonist pemafibrate or PPARγ inhibitor GW9662 was administered, Nile Red fluorescent staining was used to evaluate steatosis levels in AML12 hepatocytes, and qRT-PCR was used to detect PPARα and PPARγ gene expression. RESULTS: The results of network pharmacology analysis showed that YCHT may exert its pharmacological effect on AFLD through 312 potential targets which are involved in many signaling pathways including the PPAR signaling pathway. AFLD mice experiments results showed that YCHT markedly decreased mice serum ALT activity and serum TG levels. YCHT also significantly improved alcohol-induced hepatic injury and steatosis in mice livers. Furthermore, KEGG pathway enrichment results of RNA-Seq showed that the PPAR signaling pathway should be the most relevant pathway of YCHT in the prevention and treatment of AFLD. AFLD hepatocyte model experiment results showed that YCHT could remarkably reduce hepatocyte steatosis through reducing PPARγ expression and increasing PPARα expression. CONCLUSIONS: Our study discovered that PPARγ and PPARα are the key targets and the PPAR signaling pathway is the main signaling pathway for YCHT to prevent and treat AFLD.

12.
Cancer Gene Ther ; 28(7-8): 850-863, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-32753631

RESUMO

The aim of this study was to investigate the effect of lncRNA KCNQ1OT1 on HCC and to explore the possible underlying mechanisms. The expression levels of KCNQ1OT1, miR-149 and S1PR1 were detected by qRT-PCR assay. A dual luciferase reporter assay was used to detect the interaction between KCNQ1OT1 and miR-149, as well as miR-149 and S1PR1. The interaction between KCNQ1OT1 and miR-149 was further investigated by RNA pull-down assay. Wound healing assays and Transwell assays were carried out to determine cell migration and invasion. A xenograft tumour assay was used to validate the role of KCNQ1OT1 in vivo. KCNQ1OT1 and S1PR1 were significantly increased, but miR-149 was decreased in HCC cells. Luciferase reporter assays and RNA pull-down assays revealed that KCNQ1OT1 directly targeted miR-149. In addition, miR-149 bound to the 3'-UTR of S1PR1. Knockdown of KCNQ1OT1 or overexpression of miR-149 inhibited the invasion and migration of HCC cells. However, suppression of miR-149 could abrogate the effect of KCNQ1OT1 knockdown on the invasion and migration abilities of HCC cells. In vivo assays showed that KCNQ1OT1 knockdown suppressed tumour growth. This work suggests that lncRNA KCNQ1OT1 might act as a potential therapeutic target in HCC.


Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Receptores de Esfingosina-1-Fosfato/metabolismo , Animais , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular , Humanos , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Nus , Invasividade Neoplásica , Transfecção
13.
Anal Chem ; 92(16): 10913-10919, 2020 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-32806899

RESUMO

One of the major challenges in using upconversion nanoparticles (UCNPs) is to improve their brightness. This is particularly true for in vivo studies, as the low power excitation is required to prevent the potential photo toxicity to live cells and tissues. Here, we report that the typical NaYF4:Yb0.2,Er0.02 nanoparticles can be highly doped, and the formula of NaYF4:Yb0.8,Er0.06 can gain orders of magnitude more brightness, which is applicable to a range of mild 980 nm excitation power densities, from 0.005 W/cm2 to 0.5 W/cm2. Our results reveal that the concentration of Yb3+ sensitizer ions plays an essential role, while increasing the doping concentration of Er3+ activator ions to 6 mol % only has incremental effect. We further demonstrated a type of bright UCNPs 12 nm in total diameter for in vivo tumor imaging at a power density as low as 0.0027 W/cm2, bringing down the excitation power requirement by 42 times. This work redefines the doping concentrations to fight for the issue of concentration quenching, so that ultrasmall and bright nanoparticles can be used to further improve the performance of upconversion nanotechnology in photodynamic therapy, light-triggered drug release, optogenetics, and night vision enhancement.


Assuntos
Meios de Contraste/química , Substâncias Luminescentes/química , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Animais , Linhagem Celular Tumoral , Meios de Contraste/efeitos da radiação , Érbio/química , Érbio/efeitos da radiação , Fluoretos/química , Fluoretos/efeitos da radiação , Luz , Substâncias Luminescentes/efeitos da radiação , Medições Luminescentes , Masculino , Camundongos Endogâmicos BALB C , Nanopartículas/efeitos da radiação , Tamanho da Partícula , Carne de Porco , Suínos , Itérbio/química , Itérbio/efeitos da radiação , Ítrio/química , Ítrio/efeitos da radiação
14.
Theranostics ; 10(6): 2791-2802, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32194835

RESUMO

Development of unique theranostic nanoplatforms for tumor imaging and therapy remains an active topic in current nanomedicine. Here, we designed a novel targeted theranostic nanoplatform for enhanced T1 -weighted magnetic resonance (MR) imaging-guided chemotherapy by constructing layered double hydroxide (LDH)-stabilized ultrasmall iron oxide (Fe3O4) nanoparticles with hyaluronic acid (HA) modified as targeting agents, and anticancer drug doxorubicin (DOX) loaded with a high loading efficiency. Methods: The structure and release property of LDH-Fe3O4-HA/DOX nanoplatforms were characterized systematically. B16 melanoma cells with CD44 receptors overexpressed were used as model cells to determine the biocompatibility, targeting capability, and therapeutic efficiency of nanoplatforms. For in vivo experiment, hyaluronidase (HAase) pretreatment was combined with nanoplatform administration to investigate the MR imaging and chemotherapeutic effect. Results: The LDH-Fe3O4-HA nanohybrids possess good colloidal stability and cytocompatibility, display an r1 relaxivity 10-fold higher than the pristine ultrasmall Fe3O4 (4.38 mM-1 s-1vs 0.42 mM-1 s-1), and could release drug in a pH-responsive manner. In vitro experiments demonstrate that LDH-Fe3O4-HA/DOX nanohybrids are able to specifically target B16 cells overexpressing CD44 receptors and effectively release DOX to nucleus. In vivo results show that with the pretreatment of tumor tissue by HAase to degrade the overexpressed HA in extra-cellular matrix, the designed nanoplatforms have a better tumor penetration for significantly enhanced MR imaging of tumors and tumor chemotherapy with low side effects. Conclusion: The designed LDH-Fe3O4-HA/DOX nanohybrids may be developed as a novel targeted theranostic nanoplatform for enhanced T1 -weighted MR imaging-guided chemotherapy of CD44 receptor-overexpressing tumors.


Assuntos
Antineoplásicos , Doxorrubicina , Portadores de Fármacos/uso terapêutico , Ácido Hialurônico , Nanopartículas de Magnetita/uso terapêutico , Melanoma Experimental/tratamento farmacológico , Animais , Antineoplásicos/administração & dosagem , Linhagem Celular Tumoral , Doxorrubicina/administração & dosagem , Ácido Hialurônico/uso terapêutico , Imageamento por Ressonância Magnética , Camundongos , Camundongos Endogâmicos C57BL , Nanomedicina Teranóstica
15.
Bioconjug Chem ; 31(3): 907-915, 2020 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-32096990

RESUMO

Development of versatile nanoplatforms for cancer theranostics remains a hot topic in the area of nanomedicine. We report here a general approach to create polyethylenimine (PEI)-based hybrid nanogels (NGs) incorporated with ultrasmall iron oxide (Fe3O4) nanoparticles (NPs) and doxorubicin for T1-weighted MR imaging-guided chemotherapy of tumors. In this study, PEI NGs were first prepared using an inverse emulsion approach along with Michael addition reaction to cross-link the NGs, modified with citric acid-stabilized ultrasmall Fe3O4 NPs through 1-ethyl-3-(3-(dimethylamino)propyl) carbodiimide hydrochloride (EDC) coupling, and physically loaded with anticancer drug doxorubicin (DOX). The formed hybrid NGs possess good water dispersibility and colloidal stability, excellent DOX loading efficiency (51.4%), pH-dependent release profile of DOX with an accelerated release rate under acidic pH, and much higher r1 relaxivity (2.29 mM-1 s-1) than free ultrasmall Fe3O4 NPs (1.15 mM-1 s-1). In addition, in contrast to the drug-free NGs that possess good cytocompatibility, the DOX-loaded hybrid NGs display appreciable therapeutic activity and can be taken up by cancer cells in vitro. With these properties, the developed hybrid NGs enabled effective inhibition of tumor growth under the guidance of T1-weighted MR imaging. The developed hybrid NGs may be applied as a versatile nanoplatform for MR imaging-guided chemotherapy of tumors.


Assuntos
Doxorrubicina/química , Compostos Férricos/química , Imageamento por Ressonância Magnética , Nanogéis/química , Nanopartículas/química , Tamanho da Partícula , Polietilenoimina/química , Animais , Linhagem Celular Tumoral , Doxorrubicina/uso terapêutico , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Cinética , Camundongos
16.
Macromol Biosci ; 20(2): e1900282, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31829523

RESUMO

Nuclear medicine, involving nuclear medicine imaging and radiotherapy (RT), has become a mainstay of theranostics in the field of nanomedicine and several examples have been successfully translated into clinical practice. The combination of radionuclides with dendrimers has long been investigated in nuclear imaging, such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT), providing functional information for whole body quantitative analysis with high sensitivity due to the unique structural advantages of the dendrimer platform. Besides, radioisotopes with both therapeutic and imaging functionalities can also be combined with dendrimer platforms for theranostic applications. In this review, the recent advances in the development of radionuclide-labeled poly(amidoamine) dendrimer-based nanodevices for targeted PET, SPECT, SPECT/computed tomography, SPECT/magnetic resonance imaging of tumors, RT, as well as for SPECT-imaging-guided RT of cancer are summarized. Current restrictions hindering the clinical translation of dendrimer-based nuclear nanodevices and future prospects are also discussed.


Assuntos
Dendrímeros , Nanoestruturas , Neoplasias/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada de Emissão de Fóton Único , Dendrímeros/química , Dendrímeros/uso terapêutico , Humanos , Nanoestruturas/química , Nanoestruturas/uso terapêutico , Medicina Nuclear , Nanomedicina Teranóstica
17.
Nanoscale ; 11(46): 22343-22350, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31728477

RESUMO

The design of pH-sensitive supramolecular drug delivery systems for efficient antineoplastic drug delivery remains a huge challenge. Herein, we describe the development of pH-responsive core-shell tecto dendrimers (CSTDs) formed using benzimidazole (BM)-modified generation 3 (G3) poly(amidoamine) (PAMAM) dendrimers (G3.NHAc-BM) as a shell and ß-cyclodextrin (CD)-modified G5 PAMAM dendrimers (G5.NHAc-CD) as a core. By virtue of the host-guest recognition and pH-responsiveness of BM/ß-CD assembly, the pH-sensitive supramolecular CSTDs of G5.NHAc-CD/BM-G3.NHAc were formed and adopted to encapsulate the anticancer drug doxorubicin (DOX) via hydrophobic interactions for pH-responsive drug delivery applications. The synthesis of dendrimer derivatives and the loading of the DOX were well characterized via different methods. We show that the encapsulated DOX can be released in a sustained manner with a rapid release speed under a slightly acidic pH condition (pH < 6), which is similar to acidic tumor microenvironment. The enhanced intracellular release of DOX and improved anticancer activity of the drug-loaded pH-responsive CSTDs were demonstrated and compared with the control CSTDs formed without pH-responsiveness through flow cytometry and viability assays of cancer cells. Furthermore, the pH-sensitive CSTDs also showed efficient drug penetration and growth inhibition of three-dimensional tumor spheroids owing to the faster DOX release in an acidic pH environment. The pH-sensitive G5.NHAc-CD/BM-G3.NHAc CSTDs may be employed as a valuable intelligent delivery system for various anticancer drugs.


Assuntos
Antineoplásicos/química , Dendrímeros/química , Doxorrubicina/química , Portadores de Fármacos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Benzimidazóis/química , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/metabolismo , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , beta-Ciclodextrinas/química
18.
Chin J Nat Med ; 17(10): 792-800, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31703760

RESUMO

Polysaccharide from traditional Chinese herb, Saposhnikovia divaricata (Turcz.) Schischk. (SD) was extracted, fractionated and characterized in this work. Four fractions were prepared. Their molecular weight, monosaccharide compositions, linkage modes and structural properties were characterized with SEC-MALS-RI, HPAEC-PAD, GC-MS and NMR. SDP1 was assigned as a 1, 4-α-glucan with small amount of O-6 linked branches. SDP2 contained a big amount of the 1, 4-α-glucan and a small amount of arabinogalactan, while SDP3 possessed relatively lower amount of the 1, 4-α-glucan and a big amount of the arabinogalactan. SDP4 was defined as a pectic arabinogalactan. Four fractions showed antioxidant activities in both molecular and cellular levels and their activity was ranked as SDP4 ≈ SDP3>SDP2>SDP1. The 1, 4-α-glucan in SDP1 had the weakest, while SDP3 and SDP4 showed similar and the highest antioxidant activity. The arabinogalactan was the major component of both SDP3 and SDP4, which significantly contributed to the antioxidant activity of SDP.


Assuntos
Antioxidantes/química , Antioxidantes/isolamento & purificação , Apiaceae/química , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Animais , Antioxidantes/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Camundongos , Raízes de Plantas/química , Polissacarídeos/farmacologia , Células RAW 264.7
19.
Macromol Biosci ; 19(11): e1900272, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31531955

RESUMO

Nanogels (NGs) are 3-dimensional (3D) networks composed of hydrophilic or amphiphilic polymer chains, allowing for effective and homogeneous encapsulation of drugs, genes, or imaging agents for biomedical applications. Polyethylenimine (PEI), possessing abundant positively charged amine groups, is an ideal platform for the development of NGs. A variety of effective PEI-based NGs have been designed and much effort has been devoted to study the relationship between the structure and function of the NGs. In particular, PEI-based NGs can be prepared either using PEI as the major NG component or using PEI as a crosslinker. This review reports the recent progresses in the design of PEI-based NGs for gene and drug delivery and for bioimaging applications with a target focus to tackle the diagnosis and therapy of cancer.


Assuntos
Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Técnicas de Transferência de Genes , Nanogéis/química , Polietilenoimina/química , Animais , Tecnologia Biomédica/métodos , Tecnologia Biomédica/tendências , Portadores de Fármacos/química , Portadores de Fármacos/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Humanos , Imagem Molecular/métodos , Imagem Molecular/tendências , Nanogéis/uso terapêutico , Neoplasias/diagnóstico , Neoplasias/terapia , Polietilenoglicóis/química , Polietilenoimina/uso terapêutico , Polímeros/química , Polímeros/uso terapêutico
20.
Artif Cells Nanomed Biotechnol ; 46(sup1): 488-498, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29374979

RESUMO

In this study, we report the synthesis, characterization and utilization of 99mTc-labelled polyethylenimine-entrapped gold nanoparticles (99mTc-Au-PENPs) for dual mode single-photon emission computed tomography/computed tomography (SPECT/CT) imaging applications. Polyethylenimine (PEI) was selected as a platform to conjugate with diethylene triamine pentacetate acid (DTPA) and polyethylene glycol monomethyl ether to synthesize Au PENPs, followed by acetylation or hydroxylation modification of the remaining PEI surface amine groups and radiolabelling of 99mTc. The generated multifunctional 99mTc-Au-PENPs with different surface groups (acetyl or hydroxyl) were characterized via different methods. The Au PENPs before 99mTc labelling are colloidally stable, haemocompatibility and noncytotoxic at an Au concentration up to 100 µM. The 99mTc-labelled Au PENPs exhibit high radiochemical purity, good stability and SPECT/CT imaging performance of different organs and lymph node. The designed strategy to use the radionuclide labelling technique and PEI-facilitated versatile nanoplatform may be extended to develop various novel nanoprobes for precision imaging applications.


Assuntos
Ouro/química , Nanopartículas Metálicas/química , Polietilenoimina/química , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único/métodos , Tecnécio/química , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Marcação por Isótopo , Teste de Materiais , Camundongos , Polietilenoimina/farmacocinética , Polietilenoimina/toxicidade , Coelhos , Linfonodo Sentinela/diagnóstico por imagem , Distribuição Tecidual
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