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1.
Artigo em Inglês | MEDLINE | ID: mdl-32020504

RESUMO

Whether intra-myocardial delivery of hydrogel can prevent post-infarct heart failure (HF) in a long follow-up period, especially after it is degraded, remains unclear. In this study, Dex-PCL-HEMA/PNIPAAm (DPHP) hydrogel was delivered into peri-infarct myocardium of rat when coronary artery was ligated, while PBS was employed as control. Twelve weeks later, compared with control, left ventricle remodeling was attenuated and cardiac function was preserved; serum brain natriuretic peptide, cardiac aldosterone, and pulmonary congestion were suppressed in hydrogel group. Pro-fibrogenic mRNA increased in infarct area while decreased in remote zone, as well as hypertrophic mRNA. These data proves DPHP hydrogel suppresses ventricular remodeling and HF by promoting fibrotic healing in infarct area and inhibiting reactive fibrosis and hypertrophy in remote zone. Timely intra-myocardial hydrogel implantation is an effective strategy to inhibit post-infarct cardiac remodeling and have a long-term beneficial effect even after it has been biodegraded.

2.
Small ; 11(21): 2543-54, 2015 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-25626995

RESUMO

A novel dual-pH sensitive charge-reversal strategy is designed to deliver antitumor drugs targeting to tumor cells and to further promote the nuclei internalization by a stepwise response to the mildly acidic extracellular pH (≈6.5) of a tumor and endo/lysosome pH (≈5.0). Poly(L-lysine)-block-poly(L-leucine) diblock copolymer is synthesized and the lysine amino residues are amidated by 2,3-dimethylmaleic anhydride to form ß-carboxylic amide, making the polypeptides self-assemble into negatively charged micelles. The amide can be hydrolyzed when exposed to the mildly acidic tumor extracellular environment, which makes the micelles switch to positively charged and they are then readily internalized by tumor cells. A nuclear targeting Tat peptide is further conjugated to the polypeptide via a click reaction. The Tat is amidated by succinyl chloride to mask its positive charge and cell-penetrating function and thus to inhibit nonspecific cellular uptake. After the nanoparticles are internalized into the more acidic intracellular endo/lysosomes, the Tat succinyl amide is hydrolyzed to reactivate the Tat nuclear targeting function, promoting nanoparticle delivery into cell nuclei. This polypeptide nanocarrier facilitates tumor targeting and nuclear delivery simultaneously by simply modifying the lysine amino residues of polylysine and Tat into two different pH-sensitive ß-carboxylic amides.


Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Peptídeos/química , Transporte Ativo do Núcleo Celular , Núcleo Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacocinética , Portadores de Fármacos/química , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Micelas , Peptídeos/síntese química , Polilisina/química , Multimerização Proteica , Produtos do Gene tat do Vírus da Imunodeficiência Humana/química
3.
J Laparoendosc Adv Surg Tech A ; 24(12): 883-6, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25387325

RESUMO

The "ALPPS" (associating liver partition with portal vein ligation for staged hepatectomy) procedure enables the rapid growth of the future liver remnant and extended surgical indication to patients with an "insufficient" future liver remnant. In May 2014, a 64-year-old male patient was admitted. The computed tomography (CT) scan showed multiple right liver lesions, which were diagnosed to be hepatocellular carcinoma by liver biopsy. The future liver remnant volume after right hemihepatectomy was calculated to be 35.6% based on the CT reconstruction. Completely laparoscopic ALPPS using round-the-liver ligation, which replaced liver splitting, was performed on him. The two-stage operation was performed successfully. The future liver remnant volume increased 37.9% according to the CT scan on Day 10 after the first-stage operation. The second-stage operation was performed on Day 14 after the first-stage operation. The patient recovered uneventfully. No bile leakage occurred. Thus the round-the-liver ligation can be safely executed in laparoscopy. Completely laparoscopic ALPPS using round-the-liver ligation is feasible and could result in a rapid hypertrophy of the liver remnant in patients with liver cancer complicated with cirrhosis.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Laparoscopia/métodos , Neoplasias Hepáticas/cirurgia , Fígado/irrigação sanguínea , Procedimentos Cirúrgicos Vasculares/métodos , Biópsia , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/diagnóstico , Humanos , Ligadura/métodos , Fígado/cirurgia , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Cirrose Hepática/cirurgia , Neoplasias Hepáticas/complicações , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
4.
ACS Appl Mater Interfaces ; 6(16): 14568-75, 2014 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-25103086

RESUMO

In this paper, a novel stepwise-acid-active multifunctional mesoporous silica nanoparticle (MSN-(SA)TAT&(DMA)K11) was developed as a drug carrier. The MSN-(SA)TAT&(DMA)K11 is able to reverse its surface charge from negative to positive in the mildly acidic tumor extracellular environment. Then, the fast endo/lysosomal escape and subsequent nucleus targeting as well as intranuclear drug release can be realized after cellular internalization. Because of the difference in acidity between the tumor extracellular environment and that of endo/lysosomes, this multifunctional MSN-(SA)TAT&(DMA)K11 exhibits a stepwise-acid-active drug delivery with a tumor-specific nucleus-targeted property.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Dióxido de Silício/química , Porosidade
5.
Chem Commun (Camb) ; 50(6): 667-9, 2014 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-24281692

RESUMO

Fluorescence imaging in living cells is typically carried out using a functionalized fluorescent dye. But it often causes strong background noise under many conditions where washing is not applicable. Here, we report on a coumarin based fluorogenic probe, which can be used as a bioorthogonal-labeling tool for glycoproteins. The results indicated that the probe was able to image glycoproteins in living cells and it may also be suitable for intracellular imaging.


Assuntos
Cumarínicos/química , Corantes Fluorescentes/química , Glicoproteínas/química , Imagem Molecular/instrumentação , Citometria de Fluxo , Células HeLa , Humanos , Modelos Biológicos
6.
ACS Appl Mater Interfaces ; 5(16): 7995-8001, 2013 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-23869943

RESUMO

Mesoporous silica nanoparticles (MSNs) have proved to be an effective carrier for controlled drug release and can be functionalized easily for use as stimuli-responsive vehicles. Here, a novel intelligent drug-delivery system (DDS), camptothecin (CPT)-loaded and doxorubicin (DOX)-conjugated MSN (CPT@MSN-hyd-DOX), is reported via a facile one-pot preparation for use in synergistic chemotherapy of glioblastoma. DOX was conjugated to MSNs via acid-labile hydrazone bonds, and CPT was loaded in the pores of the MSNs. At pH 6.5 (analogous to the pH in tumor tissues), a fast DOX release was observed that was attributed to the hydrolysis of the hydrazone bonds. In addition, a further burst release of DOX was found at pH 5.0 (analogous to the pH in lyso/endosomes of tumor cells), leading to a strong synergistic effect. In all, CPT and DOX could be delivered simultaneously into tumor cells, and this intelligent DDS has great potential for tumor-trigged drug release for use in the synergistic chemotherapy of tumors.


Assuntos
Sistemas de Liberação de Medicamentos , Sinergismo Farmacológico , Glioblastoma/tratamento farmacológico , Nanopartículas/administração & dosagem , Camptotecina/administração & dosagem , Camptotecina/química , Linhagem Celular Tumoral , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Glioblastoma/patologia , Humanos , Nanopartículas/química , Porosidade , Dióxido de Silício/administração & dosagem , Dióxido de Silício/química
7.
Macromol Rapid Commun ; 32(9-10): 758-64, 2011 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-21469242

RESUMO

In this study, two asymmetrical cyclopeptides (CP1 and CP2) were designed and synthesized. The self-assembly behaviors of the asymmetrical cyclopeptides at varying pHs were investigated in terms of transmission electron microscopy (TEM), circular dichroism (CD), and Fourier transform infrared (FT-IR) spectroscopy. It was found that the self-assembly of CP1 resulted in the formation of nanofibers with α-helix conformation, while CP2 self-assembled into well-ordered nanorods with anti-parallel ß-sheet conformation. The strategy demonstrated here presents great potential for preparation of well-defined nanostructures via rationally designing the molecular structures of cyclopeptides.


Assuntos
Peptídeos Cíclicos/química , Dicroísmo Circular , Conformação Molecular , Nanoestruturas/química , Peptídeos Cíclicos/síntese química , Espectroscopia de Infravermelho com Transformada de Fourier
8.
Colloids Surf B Biointerfaces ; 85(1): 86-91, 2011 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-21087841

RESUMO

In this study, with the aim of designing an ideal anticancer drug carrier, we synthesized novel amphiphilic graft copolymers, P(Glu-alt-PEG)-graft-PCLA, based on poly(ethylene glycol) (PEG) segments and glutamic acid (Glu) units as the hydrophilic main chain, and poly(ɛ-caprolactone-co-lactide) (PCLA) as hydrophobic branches. The chemical structure of the copolymers was characterized by (1)H MNR and FT-IR. The self-assembly of the copolymers to form micelles was studied by TEM, DLS and fluorescence spectroscopy. In vitro doxorubicin controlled release studies demonstrated that these graft copolymer micelles had high drug loading capacity and good controlled released properties, demonstrating their potential as a novel anticancer drug carrier. The drug loaded graft copolymer micelles exhibited efficient inhibition of HeLa cells in in vitro studies.


Assuntos
Doxorrubicina/química , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Polímeros/química , Células HeLa , Humanos , Espectroscopia de Ressonância Magnética , Micelas , Microscopia Eletrônica de Transmissão , Poliésteres/química , Polietilenoglicóis/química , Espectrometria de Fluorescência , Espectroscopia de Infravermelho com Transformada de Fourier
9.
Pharm Res ; 27(1): 187-99, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19888639

RESUMO

PURPOSE: To study the targeting and photodynamic therapy efficiency of porphyrin and galactosyl conjugated micelles based on amphiphilic copolymer galactosyl and mono-aminoporphyrin (APP) incoporated poly(2-aminoethyl methacrylate)-polycaprolactone (Gal-APP-PAEMA-PCL). METHODS: Poly(2-aminoethyl methacrylate)-polycaprolactone (PAEMA-PCL) was synthesized by the combination of ring opening polymerization and reversible addition-fragmentation chain transfer (RAFT) polymerization, and then Gal-APP-PAEMA-PCL was obtained after conjugation of lactobionic acid and 5-(4-aminophenyl)-10,15,20-triphenylporphyrin (APP) to PAEMA-PCL. The chemical structures of the copolymers were characterized, and their biological properties were evaluated in human laryngeal carcinoma (HEp2) and human hepatocellular liver carcinoma (HepG2) cells. RESULTS: Both APP-PAEMA-PCL and Gal-APP-PAEMA-PCL did not exhibit dark cytotoxicity to HEp2 cells and HepG2 cells. However, Gal-APP-PAEMA-PCL was taken up selectively by HepG2 cells and had the higher phototoxicity effect. Both polymers preferentially localized within cellular vesicles that correlated to the lysosomes. CONCLUSIONS: The results indicated that porphyrin and galactosyl conjugated polymer micelles exhibited higher targeting and photodynamic therapy efficacy in HepG2 cells than in HEp2 cells.


Assuntos
Portadores de Fármacos/síntese química , Sistemas de Liberação de Medicamentos/métodos , Galactose/química , Fotoquimioterapia/métodos , Polímeros/síntese química , Porfirinas/síntese química , Receptor de Asialoglicoproteína/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Composição de Medicamentos/métodos , Ensaios de Seleção de Medicamentos Antitumorais , Galactose/farmacocinética , Galactose/farmacologia , Células Hep G2 , Humanos , Micelas , Modelos Biológicos , Tamanho da Partícula , Poliésteres/química , Porfirinas/farmacocinética , Porfirinas/farmacologia
10.
Macromol Biosci ; 9(12): 1219-26, 2009 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-19924686

RESUMO

In this study, a KRGDKK (Lys-Arg-Gly-Asp-Lys-Lys) peptide with a RGD sequence is utilized as a functional group to synthesize a novel thermo-sensitive hydrogel. The KRGDKK peptide prepared by a solid phase synthesis approach is coupled to the ends of a poly[(epsilon-caprolactone)-co-lactide]-poly(ethylene glycol)-poly[(epsilon-caprolactone)-co-lactide] (PCLA-PEG-PCLA) triblock copolymer to obtain peptide-PCLA-PEG-PCLA-peptide. The self-assembly behavior of both PCLA-PEG-PCLA and peptide-PCLA-PEG-PCLA-peptide copolymers in aqueous solution is investigated, and hydrogels prepared from PCLA-PEG-PCLA and peptide-PCLA-PEG-PCLA-peptide are also prepared. An in vitro cell viability study demonstrated that the peptide-PCLA-PEG-PCLA-peptide hydrogels do not exhibit an apparent cytotoxicity, which suggests that the hydrogels have promising potential as injectable drug-delivery systems. Furthermore, compared with the PCLA-PEG-PCLA hydrogels, the peptide-PCLA-PEG-PCLA-peptide hydrogels display improved mechanical properties because of hydrogen bonding between the amino groups of KRGDKK. An in vitro drug release study showed that the peptide-PCLA-PEG-PCLA-peptide hydrogels exhibit outstanding controlled release properties and the release of the drug could be sustained for more than a month without initial burst.


Assuntos
Portadores de Fármacos , Hidrogéis , Peptídeos/química , Polímeros/química , Doxorrubicina/administração & dosagem , Células HeLa , Humanos , Ligações de Hidrogênio , Espectroscopia de Ressonância Magnética , Micelas , Microscopia Eletrônica de Varredura , Tamanho da Partícula
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