NIR-Responsive Polypeptide Nanocomposite Generates NO Gas, Mild Photothermia, and Chemotherapy to Reverse Multidrug-Resistant Cancer.
Nano Lett
; 19(7): 4362-4370, 2019 07 10.
Article
em En
| MEDLINE
| ID: mdl-31199153
ABSTRACT
Multidrug resistance (MDR) of cancers that results from overexpression of a P-glycoprotein (P-gp) transporter mainly causes chemotherapy (CT) failure and hinders clinical transitions of current polypeptide nanomedicines. Herein, a novel polypeptide nanocomposite PNOC-PDA that integrates heat-sensitive NO gas delivery and photothermal conversion attributes can overcome MDR and maximize CT; meanwhile the optimized CT and intracellular high-concentration NO gas can assist a mild photothermal therapy (PTT) to eradicate cancer cells. The triple therapies produced a superior and synergistic effect on MDR-reversal and killing MCF-7/ADR in vitro, and the P-gp expression level was downregulated to 46%, as confirmed by means of MTT, Western blot, flow cytometry, and confocal laser scanning microscopy. Significantly, by using one intravenous injection of PNOC-PDA/DOX and a single near-infrared irradiation, the triple therapies of mild PTT, NO gas therapy, and CT achieved complete MCF-7/ADR tumor ablation without skin damage, scarring, and tumor recurrence within 30 days. This work provides a versatile method for the fabrication of NIR-responsive polypeptide nanocomposite with intrinsic photothermal conversion and NO-releasing attributes, opening up a new avenue for reversing MDR in tumors.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
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Fototerapia
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Resistência a Múltiplos Medicamentos
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Resistencia a Medicamentos Antineoplásicos
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Nanocompostos
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Hipertermia Induzida
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Neoplasias Experimentais
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Óxido Nítrico
Limite:
Animals
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Humans
Idioma:
En
Revista:
Nano Lett
Ano de publicação:
2019
Tipo de documento:
Article