Molecular bottlebrush prodrugs as mono- and triplex combination therapies for multiple myeloma.
Journal
Nature nanotechnology
ISSN: 1748-3395
Titre abrégé: Nat Nanotechnol
Pays: England
ID NLM: 101283273
Informations de publication
Date de publication:
02 2023
02 2023
Historique:
received:
26
02
2021
accepted:
06
12
2022
pubmed:
27
1
2023
medline:
3
3
2023
entrez:
26
1
2023
Statut:
ppublish
Résumé
Cancer therapies often have narrow therapeutic indexes and involve potentially suboptimal combinations due to the dissimilar physical properties of drug molecules. Nanomedicine platforms could address these challenges, but it remains unclear whether synergistic free-drug ratios translate to nanocarriers and whether nanocarriers with multiple drugs outperform mixtures of single-drug nanocarriers at the same dose. Here we report a bottlebrush prodrug (BPD) platform designed to answer these questions in the context of multiple myeloma therapy. We show that proteasome inhibitor (bortezomib)-based BPD monotherapy slows tumour progression in vivo and that mixtures of bortezomib, pomalidomide and dexamethasone BPDs exhibit in vitro synergistic, additive or antagonistic patterns distinct from their corresponding free-drug counterparts. BPDs carrying a statistical mixture of three drugs in a synergistic ratio outperform the free-drug combination at the same ratio as well as a mixture of single-drug BPDs in the same ratio. Our results address unanswered questions in the field of nanomedicine, offering design principles for combination nanomedicines and strategies for improving current front-line monotherapies and combination therapies for multiple myeloma.
Identifiants
pubmed: 36702954
doi: 10.1038/s41565-022-01310-1
pii: 10.1038/s41565-022-01310-1
pmc: PMC10032145
mid: NIHMS1877310
doi:
Substances chimiques
Bortezomib
69G8BD63PP
Prodrugs
0
Dexamethasone
7S5I7G3JQL
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
184-192Subventions
Organisme : NCI NIH HHS
ID : R01 CA220468
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA205954
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : 1R01CA220468-01
Commentaires et corrections
Type : CommentIn
Type : ErratumIn
Type : ErratumIn
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature Limited.
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