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1.
Int J Nanomedicine ; 12: 2733-2748, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28442903

RESUMO

Nonspecific targeting, large doses and phototoxicity severely hamper the clinical effect of photodynamic therapy (PDT). In this work, superparamagnetic Fe3O4 mesoporous silica nanoparticles grafted by pH-responsive block polymer polyethylene glycol-b-poly(aspartic acid) (PEG-b-PAsp) were fabricated to load the model photosensitizer rose bengal (RB) in the aim of enhancing the efficiency of PDT. Compared to free RB, the nanocomposites (polyethylene glycol-b-polyaspartate-modified rose bengal-loaded magnetic mesoporous silica [RB-MMSNs]) could greatly enhance the cellular uptake due to their effective endocytosis by mouse melanoma B16 cell and exhibited higher induced apoptosis although with little dark toxicity. RB-MMSNs had little dark toxicity and even much could be facilitated by magnetic field in vitro. RB-MMSNs demonstrated 10 times induced apoptosis efficiency than that of free RB at the same RB concentration, both by cell counting kit-8 (CCK-8) result and apoptosis detection. Furthermore, RB-MMSNs-mediated PDT in vivo on tumor-bearing mice showed steady physical targeting of RB-MMSNs to the tumor site; tumor volumes were significantly reduced in the magnetic field with green light irradiation. More importantly, the survival time of tumor-bearing mice treated with RB-MMSNs was much prolonged. Henceforth, polyethylene glycol-b-polyaspartate-modified magnetic mesoporous silica (MMSNs) probably have great potential in clinical cancer photodynamic treatment because of their effective and low-toxic performance as photosensitizers' vesicles.


Assuntos
Nanocompostos/química , Nanocompostos/uso terapêutico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Endocitose/efeitos dos fármacos , Óxido Ferroso-Férrico/química , Concentração de Íons de Hidrogênio , Magnetismo , Masculino , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos C57BL , Nanopartículas/química , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Polietilenoglicóis/química , Rosa Bengala/administração & dosagem , Rosa Bengala/análogos & derivados , Rosa Bengala/química , Dióxido de Silício/química
2.
Int J Nanomedicine ; 11: 1793-806, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27175077

RESUMO

In this study, a highly effective transmembrane delivery vehicle based on PEGylated oxidized mesoporous carbon nanosphere (oMCN@PEG) was successfully fabricated in a facile strategy. oMCN@PEG exhibited a narrow size distribution of 90 nm, excellent hydrophilicity, good biocompatibility, and a very high loading efficiency for doxorubicin (DOX). The drug system (oMCN@DOX@PEG) exhibited excellent stability under neutral pH conditions, but with dramatic releases of DOX at reduced pH conditions. Pharmacokinetics study revealed that oMCN@DOX@PEG could prolong the circulation of DOX in the blood stream. The endocytosis, cytotoxicity, and anticancer effect in vitro and in vivo of the drug-loaded nanoparticles were also evaluated. Our results showed that the nanoparticles efficiently penetrated the membrane of tumor cells, subsequently released drugs, and efficiently inhibited the growth of cancer cells both in vitro and in vivo. Especially, oMCN@DOX@PEG also exhibited significant antimetastasis effect in advanced stage of malignant cancer, improving the survival time of tumor-bearing mice. The results suggested that oMCN@PEG might be a promising anticancer drug delivery vehicle for cancer therapy.


Assuntos
Carbono/química , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Interações Hidrofóbicas e Hidrofílicas , Nanosferas/química , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/sangue , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Lewis/sangue , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Carcinoma Pulmonar de Lewis/patologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Permeabilidade da Membrana Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/sangue , Doxorrubicina/farmacocinética , Portadores de Fármacos , Liberação Controlada de Fármacos , Difusão Dinâmica da Luz , Humanos , Masculino , Camundongos Endogâmicos C57BL , Nanosferas/ultraestrutura , Oxirredução , Polietilenoglicóis/química , Porosidade , Ratos Sprague-Dawley
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