An intelligent hypoxia-relieving chitosan-based nanoplatform for enhanced targeted chemo-sonodynamic combination therapy on lung cancer.
Carbohydr Polym
; 274: 118655, 2021 Nov 15.
Article
en En
| MEDLINE
| ID: mdl-34702474
ABSTRACT
The clinical efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs)-based targeted molecular therapies (TMT) is inevitably hampered by the development of acquired drug resistance in non-small cell lung cancer (NSCLC) treatment. Sonodymanic therapy (SDT) is a promising new cancer treatment approach, but its effects are restricted by tumor hypoxia. Herein, a nanoplatform fabricated by erlotinib-modified chitosan loading sonosensitizer hematoporphyrin (HP) and oxygen-storing agent perfluorooctyl bromide (PFOB), namely CEPH, was developed to deliver HP to erlotinib-sensitive cells. CEPH with ultrasound could alleviate hypoxia inside the three-dimensional multicellular tumor spheroids, suppress NSCLC cell growth under normoxic or hypoxic condition, and enhance TMT/SDT synergistic effects through elevated production of reactive oxygen species, decrease of mitochondrial membrane potential, and down-regulation of the expression of the proteins EGFR, p-EGFR, and HIF-1α. Hence, CEPH could be a potential nanoplatform to improve the efficacy of oxygen-dependent SDT and overcome hypoxia-induced TMT resistance for enhanced synergistic TMT/SDT.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Carcinoma de Pulmón de Células no Pequeñas
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Quitosano
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Quimioterapia Combinada
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Terapia Molecular Dirigida
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Clorhidrato de Erlotinib
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Neoplasias Pulmonares
Límite:
Humans
Idioma:
En
Revista:
Carbohydr Polym
Año:
2021
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
ENGLAND
/
ESCOCIA
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GB
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GREAT BRITAIN
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INGLATERRA
/
REINO UNIDO
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SCOTLAND
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UK
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UNITED KINGDOM