Albumin-based nanostructures for uveal melanoma treatment.
Animals
Feeder Cells
Humans
Melanoma
/ drug therapy
Mice
Mice, Nude
Morpholines
/ chemistry
Nanostructures
/ chemistry
Neoplasm Proteins
/ antagonists & inhibitors
Serum Albumin, Human
/ chemistry
TOR Serine-Threonine Kinases
/ antagonists & inhibitors
Uveal Neoplasms
/ drug therapy
Xenograft Model Antitumor Assays
AZD8055
Albumin-based nanostructures
Controlled-release
Nanomedicine
Uveal melanoma
Journal
Nanomedicine : nanotechnology, biology, and medicine
ISSN: 1549-9642
Titre abrégé: Nanomedicine
Pays: United States
ID NLM: 101233142
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
25
06
2020
revised:
21
02
2021
accepted:
18
03
2021
pubmed:
2
4
2021
medline:
19
1
2022
entrez:
1
4
2021
Statut:
ppublish
Résumé
Uveal melanoma (UM) is an intraocular tumor which is almost lethal at the metastatic stage due to the lack of effective treatments. In this regard, we have developed an albumin-based nanostructure (ABN) containing AZD8055 (ABN-AZD), which is a potent mTOR kinase inhibitor, for its efficient delivery to the tumors. The drug has been conjugated to ABN using tailored linkers that have a disulfide moiety, allowing its release selectively and effectively in the presence of an elevated concentration of glutathione, such as inside the tumoral cells. Our therapeutic approach induced significant cellular toxicity in uveal melanoma cells, but not in non-tumoral keratinocytes, highlighting the excellent selectivity of the system. In addition, these nanostructures showed excellent activity in vivo, decreasing the tumor surface compared to the free AZD8055 in mice models. Remarkably, the results obtained were achieved employing a dose 23 times lower than those used in previous reports.
Identifiants
pubmed: 33794371
pii: S1549-9634(21)00034-4
doi: 10.1016/j.nano.2021.102391
pii:
doi:
Substances chimiques
Morpholines
0
Neoplasm Proteins
0
(5-(2,4-bis((3S)-3-methylmorpholin-4-yl)pyrido(2,3-d)pyrimidin-7-yl)-2-methoxyphenyl)methanol
970JJ37FPW
MTOR protein, human
EC 2.7.1.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Serum Albumin, Human
ZIF514RVZR
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
102391Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.