A novel peptide-drug conjugate for glioma-targeted drug delivery.
J Control Release
; 369: 722-733, 2024 May.
Article
de En
| MEDLINE
| ID: mdl-38583575
ABSTRACT
The existence of the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB) greatly limits the application of chemotherapy in glioma. To address this challenge, an optimal drug delivery system must efficiently cross the BBB/BBTB and specifically deliver therapeutic drugs into glioma cells while minimizing systemic toxicity. Here we demonstrated that glucose-regulated protein 78 (GRP78) and dopamine receptor D2 were highly expressed in patient-derived glioma tissues, and dopamine receptors were highly expressed on the BBB. Subsequently, we synthesized a novel "Y"-shaped peptide and compared the effects of different linkers on the receptor affinity and targeting ability of the peptide. A peptide-drug conjugate (pHA-AOHX-VAP-doxorubicin conjugate, pHA-AOHX-VAP-DOX) with a better affinity for glioma cells and higher solubility was derived for glioma treatment. pHA-AOHX-VAP-DOX could cross both BBB and BBTB via dopamine receptor and GRP78 receptor, and finally target glioma cells, significantly prolonging the survival time of nude mice bearing intracranial glioma. Furthermore, pHA-AOHX-VAP-DOX significantly reduced the toxicity of DOX and increased the maximum tolerated dose (MTD). Collectively, this work paves a new avenue for overcoming multiple barriers and effectively delivering chemotherapeutic agents to glioma cells while providing key evidence to identify potential receptors for glioma-targeted drug delivery.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Peptides
/
Tumeurs du cerveau
/
Barrière hémato-encéphalique
/
Doxorubicine
/
Systèmes de délivrance de médicaments
/
Chaperonne BiP du réticulum endoplasmique
/
Gliome
/
Souris nude
Limites:
Animals
/
Humans
/
Male
Langue:
En
Journal:
J Control Release
/
J. control. release
/
Journal of controlled release
Sujet du journal:
FARMACOLOGIA
Année:
2024
Type de document:
Article
Pays d'affiliation:
Chine
Pays de publication:
Pays-Bas