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1.
Eur J Med Chem ; 142: 416-423, 2017 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-28870452

RESUMO

In this study, we propose doxorubicin (DOX) loaded oligonucleotides (ONTs) attached to gold nanoparticles (AuNPs) as a drug delivery system for cancer chemotherapy. DOX is one of the representative cancer chemotherapy agents and is widely used by many researchers as a chemotherapy agent in the drug delivery system. Due to the advantages of AuNPs such as simple steps in synthesis, high surface-area-to-volume ratio, and biocompatibility, we utilized AuNPs as drug delivery vehicle. AuNPs were synthesized by chemical reduction to be 13 nm diameter. The G-C rich oligonucleotides were used both for drug loading sites and AuNPs capping agents. 80% of DOX in solution could be bound to ONTs on AuNPs to became DOX-loaded AuNPs coated with ONTs (Doxorubicin-Oligomer-AuNP, DOA), and about 28% of loaded DOX was released from the as-prepared DOA. Confocal microscopy observation showed that DOA was well transported into cells, and finally the DOX was released into the cell nucleus. The drug's efficacies such as in vitro cytotoxicity and in vivo tumor growth inhibition were demonstrated with SW480 colon cancer cell line and a xenograft mouse model. MTT assay was performed to see the cytotoxicity effect on SW480 cells treated with DOA for 24 h, and the cell viability was determined to be 41.77% (p < 0.001). When DOA was administered regularly to a tumor bearing mouse, the tumor growth inhibition degree was examined by measuring the tumor size. The treatment-control (T/C) ratio was found to be 0.69. Thus, our results suggest the use of DOAs as promising drug delivery systems for colorectal cancer therapy.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Doxorrubicina/administração & dosagem , Portadores de Fármacos/química , Ouro/química , Nanopartículas Metálicas/química , Oligonucleotídeos/química , Animais , Antibióticos Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Colo/efeitos dos fármacos , Colo/patologia , Neoplasias Colorretais/patologia , Doxorrubicina/uso terapêutico , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Camundongos Endogâmicos BALB C , Reto/efeitos dos fármacos , Reto/patologia
2.
Talanta ; 147: 453-9, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26592632

RESUMO

Negatively charged multi-walled carbon nanotubes (MWCNTs) were prepared using simple sonication technique with non-toxic citric acid (CA) for the electrochemical detection of dopamine (DA). CA/MWCNTs were placed on glassy carbon (GC) electrodes by drop-casting method and then electrochemical determinations of DA were performed in the presence of highly concentrated ascorbic acid (AA). For the comparison of the charge effect on MWCNTs surface, positively charged polyethyleneimine (PEI)/MWCNT/GC electrode and pristine MWCNT/GC electrode were also prepared. Contrary to conventional GC electrode, all three types of MWCNT modified electrodes (CA/MWCNT/GC, PEI/MWCNT/GC, and pristine MWCNT/GC) can discriminate ~µM of DA from 1mM AA using cyclic voltammetry (CV) and differential pulse voltammetry (DPV) due to the inherent electrocatalytic effect of MWCNTs. Compared to positively charged PEI/MWCNT/GC and pristine MWCNT/GC electrodes, negatively charged CA/MWCNT/GC electrode remarkably enhanced the electrochemical sensitivity and selectivity of DA, showing the linear relationship between DPV signal and DA concentration in the range of 10-1000nM even in the presence of ~10(5) times concentrated AA, which is attributed to the synergistic effect of the electrostatic interaction between cationic DA molecules and negatively charged MWCNTs and the inherent electrocatalytic property of MWCNT. As a result, the limit of detection (LOD) of DA for CA/MWCNT/GC electrode was 4.2nM, which is 5.2 and 16.5 times better than those for MWCNT/GC electrode and PEI/MWCNT/GC electrode even in the presence of 1mM AA. This LOD value for DA at CA/MWCNT/GC electrode is one of the lowest values compared to the previous reports and is low enough for the early diagnosis of neurological disorder in the presence of physiological AA concentration (~0.5mM). In addition, the high selectivity and sensitivity of DA at CA/MWCNT/GC electrode were well kept even in the presence of both 1mM AA and 10µM uric acid (UA) as similar as neurophysiological concentration.


Assuntos
Ácido Cítrico/química , Dopamina/análise , Nanotubos de Carbono/química , Polietilenoimina/química , Ácido Ascórbico/química , Carbono/química , Dopamina/química , Técnicas Eletroquímicas , Eletrodos , Química Verde , Microscopia Eletrônica de Varredura , Nanotubos de Carbono/ultraestrutura , Espectroscopia de Infravermelho com Transformada de Fourier , Ácido Úrico/química
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