Membrane Permeability and Responsiveness Drive Performance: Linking Structural Features with the Antitumor Effectiveness of Doxorubicin-Loaded Stimuli-Triggered Polymersomes.
Biomacromolecules
; 25(7): 4192-4202, 2024 Jul 08.
Article
in En
| MEDLINE
| ID: mdl-38917475
ABSTRACT
The permeability and responsiveness of polymer membranes are absolutely relevant in the design of polymersomes for cargo delivery. Accordingly, we herein correlate the structural features, permeability, and responsiveness of doxorubicin-loaded (DOX-loaded) nonresponsive and stimuli-responsive polymersomes with their in vitro and in vivo antitumor performance. Polymer vesicles were produced using amphiphilic block copolymers containing a hydrophilic poly[N-(2-hydroxypropyl)methacrylamide] (PHPMA) segment linked to poly[N-(4-isopropylphenylacetamide)ethyl methacrylate] (PPPhA, nonresponsive block), poly[4-(4,4,5,5-tetra-methyl-1,3,2-dioxaborolan-2-yl)benzyl methacrylate] [PbAPE, reactive oxygen species (ROS)-responsive block], or poly[2-(diisopropylamino)ethyl methacrylate] (PDPA, pH-responsive block). The PDPA-based polymersomes demonstrated outstanding biological performance with antitumor activity notably enhanced compared to their counterparts. We attribute this behavior to a fast-triggered DOX release in acidic tumor environments as induced by pH-responsive polymersome disassembly at pH < 6.8. Possibly, an insufficient ROS concentration in the selected tumor model attenuates the rate of ROS-responsive vesicle degradation, whereas the nonresponsive nature of the PPPhA block remarkably impacts the performance of such potential nanomedicines.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Doxorubicin
Limits:
Animals
/
Humans
Language:
En
Journal:
Biomacromolecules
Journal subject:
BIOLOGIA MOLECULAR
Year:
2024
Document type:
Article
Affiliation country: