pH-Responsive Micellar Nanoparticles for the Delivery of a Self-Amplifying ROS-Activatable Prodrug.
Biomacromolecules
; 25(3): 1775-1789, 2024 Mar 11.
Article
in En
| MEDLINE
| ID: mdl-38377594
ABSTRACT
The objective of this study is to enhance the therapeutic efficacy of the anticancer drug, camptothecin (CPT) via a nanoparticle (NP) formulation using a novel amphiphilic biopolymer. We have designed a dimeric prodrug of CPT with the ability to self-amplify and respond to reactive oxygen species (ROS). For this, we incorporated the intracellular ROS generator cinnamaldehyde into a ROS-cleavable thioacetal (TA) linker to obtain the dimeric prodrug of CPT (DCPT(TA)). For its efficient NP delivery, a pH-responsive block copolymer of acetalated dextran and poly(2-ethyl-2-oxazoline) (AcDex-b-PEOz) was synthesized. The amphiphilic feature of the block copolymer enables its self-assembly into micellar NPs and results in high prodrug loading capacity and a rapid release of the prodrug under acidic conditions. Upon cellular uptake by HeLa cells, DCPT(TA)-loaded micellar NPs induce intracellular ROS generation, resulting in accelerated prodrug activation and enhanced cytotoxicity. These results indicate that this system holds significant potential as an effective prodrug delivery strategy in anticancer treatment.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Prodrugs
/
Nanoparticles
Limits:
Humans
Language:
En
Journal:
Biomacromolecules
Journal subject:
BIOLOGIA MOLECULAR
Year:
2024
Type:
Article
Affiliation country:
Australia