VLA4-Targeted Nanoparticles Hijack Cell Adhesion-Mediated Drug Resistance to Target Refractory Myeloma Cells and Prolong Survival.
Animals
Camptothecin
/ therapeutic use
Cell Adhesion
Cell Line, Tumor
Dexamethasone
/ pharmacology
Drug Resistance, Neoplasm
Humans
Integrin alpha4beta1
/ metabolism
Melphalan
/ pharmacology
Mice
Mice, Inbred C57BL
Multiple Myeloma
/ drug therapy
Nanoparticles
/ metabolism
Topoisomerase I Inhibitors
/ therapeutic use
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
01 04 2021
01 04 2021
Historique:
received:
21
07
2020
revised:
20
10
2020
accepted:
15
12
2020
pubmed:
24
12
2020
medline:
11
3
2022
entrez:
23
12
2020
Statut:
ppublish
Résumé
In multiple myeloma, drug-resistant cells underlie relapse or progression following chemotherapy. Cell adhesion-mediated drug resistance (CAM-DR) is an established mechanism used by myeloma cells (MMC) to survive chemotherapy and its markers are upregulated in residual disease. The integrin very late antigen 4 (VLA4; α We synthetized 20 nm VLA4-targeted micellar nanoparticles (V-NP) carrying DiI for tracing or a novel camptothecin prodrug (V-CP). Human or murine MMCs, alone or with stroma, and immunocompetent mice with orthotopic multiple myeloma were used to track delivery of NPs and response to treatments. V-NPs selectively delivered their payload to MMCs V-CP may be a safe and effective strategy to prevent or treat relapsing or refractory myeloma. V-NP targeting of resistant cells may suggest a new approach to environment-induced resistance in cancer.
Identifiants
pubmed: 33355244
pii: 1078-0432.CCR-20-2839
doi: 10.1158/1078-0432.CCR-20-2839
pmc: PMC8026499
mid: NIHMS1657182
doi:
Substances chimiques
Integrin alpha4beta1
0
Topoisomerase I Inhibitors
0
Dexamethasone
7S5I7G3JQL
Melphalan
Q41OR9510P
Camptothecin
XT3Z54Z28A
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1974-1986Subventions
Organisme : NCI NIH HHS
ID : R50 CA211466
Pays : United States
Organisme : NIAMS NIH HHS
ID : P30 AR074992
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA216840
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA199092
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA154737
Pays : United States
Informations de copyright
©2020 American Association for Cancer Research.
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