Tumor Microenvironment-Responsive Nanococktails for Synergistic Enhancement of Cancer Treatment via Cascade Reactions.
ACS Appl Mater Interfaces
; 13(4): 4861-4873, 2021 Feb 03.
Article
em En
| MEDLINE
| ID: mdl-33471499
ABSTRACT
A combination treatment strategy that relies on the synergetic effects of different therapeutic approaches has been considered to be an effective method for cancer therapy. Herein, a chemotherapeutic drug (doxorubicin, Dox) and a manganese ion (Mn2+) were co-loaded into regenerated silk fibroin-based nanoparticles (NPs), followed by the surface conjugation of phycocyanin (PC) to construct tumor microenvironment-activated nanococktails. The resultant PC-Mn@Dox-NPs showed increased drug release rates by responding to various stimulating factors (acidic pH, hydrogen peroxide (H2O2), and glutathione), revealing that they could efficiently release the payloads (Dox and Mn2+) in tumor cells. The released Dox could not only inhibit the growth of tumor cells but also generated a large amount of H2O2. The elevated H2O2 was decomposed into the highly harmful hydroxyl radicals and oxygen through an Mn2+-mediated Fenton-like reaction. Furthermore, the generated oxygen participated in photodynamic therapy (PDT) and produced abundant singlet oxygen. Our investigations demonstrate that these PC-Mn@Dox-NPs exhibit multiple bioresponsibilities and favorable biosafety. By integrating Dox-induced chemotherapy, Mn2+-mediated chemodynamic therapy, and PC-based PDT via cascade reactions, PC-Mn@Dox-NPs achieved enhanced in vitro and in vivo anticancer efficacies compared to all the mono- or dual-therapeutic approaches. These findings reveal that PC-Mn@Dox-NPs can be exploited as a promising nanococktail for cascade reaction-mediated synergistic cancer treatment.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ficocianina
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Doxorrubicina
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Fármacos Fotossensibilizantes
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Manganês
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Antibióticos Antineoplásicos
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Neoplasias
Limite:
Animals
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Humans
Idioma:
En
Revista:
ACS Appl Mater Interfaces
Ano de publicação:
2021
Tipo de documento:
Article