Enhancing the tumor penetration of multiarm polymers by collagenase modification.
Biomater Sci
; 12(9): 2302-2311, 2024 Apr 30.
Article
em En
| MEDLINE
| ID: mdl-38497169
ABSTRACT
Tumor penetration is a critical determinant of the therapy efficacy of nanomedicines. However, the dense extracellular matrix (ECM) in tumors significantly hampers the deep penetration of nanomedicines, resulting in large drug-untouchable areas and unsatisfactory therapy efficacy. Herein, we synthesized a third-generation PAMAM-cored multiarm copolymer and modified the polymer with collagenase to enhance its tumor penetration. Each arm of the copolymer was a diblock copolymer of poly(glutamic acid)-b-poly(carboxybetaine), in which the polyglutamic acid block with abundant side groups was used to link the anticancer agent doxorubicin through the pH-sensitive acylhydrazone linkage, and the zwitterionic poly(carboxybetaine) block provided desired water solubility and anti-biofouling capability. The collagenase was conjugated to the ends of the arms via the thiol-maleimide reaction. We demonstrated that the polymer-bound collagenase could effectively catalyze the degradation of the collagen in the tumor ECM, and consequently augmented the tumor penetration and antitumor efficacy of the drug-loaded polymers.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doxorrubicina
/
Colagenases
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article