Synthesis and photodynamic activities of integrin-targeting silicon(IV) phthalocyanine-cRGD conjugates.
Eur J Med Chem
; 155: 24-33, 2018 Jul 15.
Article
em En
| MEDLINE
| ID: mdl-29852329
ABSTRACT
A series of novel symmetric or unsymmetric silicon (IV) phthalocyanines axially substituted with cyclic Arg-Gly-Asp (cRGD) ligands through different ethylene glycol chains have been synthesized by a facile and mild "click" reaction. All the compounds show efficient photosensitizing activities in N,N-dimethylformamide, and are essentially non-aggregated in RPMI 1640 medium with 0.05% Cremophor EL. Owing to the presence of two cRGD ligands, the conjugate 6b exhibits highest selectivity toward αvß3+ HT-29â¯cells in photocytotoxicities. It shows higher cellular uptake and ROS generation efficiency toward the αvß3+ HT-29â¯cells compared with that of αvß3- MCF-7â¯cells. The competitive cellular uptake and subcellular localization indicate that 6b is internalized mainly through integrin-mediated endocytosis. In addition, the in vivo studies showed that 6b can mainly accumulate in tumor sites and show a significant PDT effect resulting in 75% tumor growth inhibition. The results indicate that 6b is a highly promising photosensitizer for targeted photodynamic therapy.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peptídeos Cíclicos
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Fotoquimioterapia
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Silício
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Integrinas
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Fármacos Fotossensibilizantes
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Indóis
Limite:
Animals
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Humans
Idioma:
En
Revista:
Eur J Med Chem
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China