Harnessing the CD44-targeted delivery of self-assembled hyaluronan nanogel to reverse the antagonism between Cisplatin and Gefitinib in NSCLC cancer therapy.
Carbohydr Polym
; 344: 122521, 2024 Nov 15.
Article
em En
| MEDLINE
| ID: mdl-39218565
ABSTRACT
The combination of the standard platinum-based chemotherapy with EGFR-tyrosine kinase inhibitor Gefitinib (Gef) principally boosts the anticancer efficacy of advanced non-small cell lung cancer (NSCLC) through non-overlapping mechanisms of action, however the clinical trials of cisplatin (Cis) and Gef combination failed to show a therapeutic improvement likely due to compromised cellular influx of Cis with the Gef interference. To overcome the antagonism between Cis and Gef in anti-NSCLC therapy, here we demonstrated a self-targeted hyaluronan (HA) nanogel to facilitate the anticancer co-delivery by utilizing the HA's intrinsic targeting towards CD44, a receptor frequently overexpressed on lung cancer cells. The co-assembly between HA, Cis and Gef generated a HA/Cis/Gef nanogel of 177.8 nm, featuring a prolonged drug release. Unlike the Gef inhibited the Cis uptake, the HA/Cis/Gef nanogel efficiently facilitated the drug internalization through CD44-targeted delivery as verified by HA competition and CD44 knocking down in H1975 NSCLC model both in vitro and in vivo. Moreover, the HA/Cis/Gef nanogel significantly improved the anticancer efficacy and meanwhile diminished the side effects in reference to the combination of free Cis and Gef. This CD44-targeted HA/Cis/Gef nanogel provided a potent strategy to advance the platinum-based combination therapy towards optimized NSCLC therapy.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cisplatino
/
Carcinoma Pulmonar de Células não Pequenas
/
Receptores de Hialuronatos
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Gefitinibe
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Nanogéis
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Ácido Hialurônico
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Neoplasias Pulmonares
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Antineoplásicos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Carbohydr Polym
Ano de publicação:
2024
Tipo de documento:
Article
País de publicação:
Reino Unido