NO-dependent vasodilation and deep tumor penetration for cascade-amplified antitumor performance.
J Control Release
; 347: 389-399, 2022 07.
Article
em En
| MEDLINE
| ID: mdl-35569586
ABSTRACT
Nonspecific biodistribution and poor permeability of conventional therapeutic agents in solid tumors severely compromised the antitumor efficacy. Herein, we report a cascade tumor therapeutic nanoplatform consisting of docosahexaenoic acid (DHA) and nicorandil (NI), namely DNP, to specifically produce cytotoxic agents in tumor cells as well as dilating blood vessels to increase the intratumoral oxidative stress levels. The DHA embedded in the membrane could generate reactive oxygen species (ROS) meanwhile NI produced nitric oxide (NO) in response to intracellular glutathione (GSH) in tumors. Notably, the two functional species could further react in situ to form a more tumoricidal reactive nitrogen species (RNS), causing selectively cascade amplification of antitumor performance. In addition, NO-induced vasodilation could consequently result in a series of functions, including hypoxia relief and deep tumor transportation. In general, we anticipate that the DNP could show great potential for tumor-specific treatment by selectively producing RNS precursors in response to the interior environment of tumor cells for hypoxia normalization and tumor inhibition.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vasodilatação
/
Óxido Nítrico
Limite:
Humans
Idioma:
En
Revista:
J Control Release
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China