Dual-Prodrug-Based Hyaluronic Acid Nanoplatform Provides Cascade-Boosted Drug Delivery for Oxidative Stress-Enhanced Chemotherapy.
ACS Appl Mater Interfaces
; 16(38): 50459-50473, 2024 Sep 25.
Article
em En
| MEDLINE
| ID: mdl-39258403
ABSTRACT
Insufficient drug accumulation in tumors severely limits the antitumor efficiency of hyaluronic acid (HA) nanomedicine in solid tumors due to superficial penetration depth, low cell uptake, and nonspecific drug release. Hence, we constructed a dual NO prodrug (alkynyl-JSK) and doxorubicin prodrug (cis-DOX)-conjugated HA nanoparticle (HA-DOX-JSK NPs), which achieved cascade-boosted drug delivery efficiency based on a relay strategy of NO-mediated deep tumor penetrationâHA target CD44 tumor cell uptakeâtumor microenvironment (TME)-responsive drug release. The nanoparticle demonstrated sustained and locoregionally GSH/GST-triggered NO release and GSH/pH-responsive DOX release in the tumor. The released NO first mediated collagen degradation, causing deep tumor penetration of nanoparticles in the dense extracellular matrix. Immediately, HA was relayed to enhance CD44-targeted tumor cell uptake, and then, the nanoparticles were finally triggered by specific TME to release DOX and NO in the deep tumor. Relying on the relayed delivery strategy, a significant improvement of DOX accumulation in tumors was realized. Moreover, NO depleted GSH-induced intracellular reactive oxygen species, enhancing DOX chemotherapy. Based on this strategy, the tumor inhibition rate in breast cancer was up to 87.8% in vivo. The relay drug-delivery HA system would greatly cascade-boost drug accumulation in deep tumors for efficient solid tumor therapy.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pró-Fármacos
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Doxorrubicina
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Estresse Oxidativo
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Nanopartículas
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Ácido Hialurônico
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article