Tumor permeable self-delivery nanodrug targeting mitochondria for enhanced chemotherapy.
J Control Release
; 361: 792-802, 2023 09.
Article
in En
| MEDLINE
| ID: mdl-37595665
Drug self-delivery systems (DSDSs) have been extensively exploited to enhance drug loading capacity and avoid excipient-related toxicity issues. However, deficient tumor targeting, inferior tumor permeability, prominent burst release, and nonspecific subcellular distribution remain major obstacles. Herein, we reported a ROS-responsive amphiphilic prodrug (CPT-S-NO) synthesized by the conjugation of zwitterionic tertiary amine-oxide (TAO) moiety and hydrophobic camptothecin (CPT) through a thioether linkage, which formed a nanoparticulate DSDS in an aqueous solution. CPT-S-NO, compared with CPT-11 and the water-soluble TAO-modified CPT prodrug (CPT-NO), exhibited prolonged blood circulation, enhanced tumor accumulation, deep tumor penetration, efficient mitochondrial targeting, and ROS-activated drug release to induce mitochondrial dysfunction, corporately conducing to the superior antitumor efficacy in vivo. This TAO decoration strategy promises potential applications in designing multipotent DSDSs for various drugs.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Prodrugs
/
Nanoparticles
/
Neoplasms
Limits:
Humans
Language:
En
Journal:
J Control Release
Journal subject:
FARMACOLOGIA
Year:
2023
Document type:
Article
Country of publication: