Co-assembly of polymeric conjugates sensitizes neoadjuvant chemotherapy of triple-negative breast cancer with reduced systemic toxicity.
Acta Biomater
; 175: 329-340, 2024 02.
Article
em En
| MEDLINE
| ID: mdl-38135204
ABSTRACT
Rational design of polymeric conjugates could greatly potentiate the combination therapy of solid tumors. In this study, we designed and prepared two polymeric conjugates (HT-DTX and PEG-YC-1), whereas the drugs were attached to the PEG via a linker sensitive to cathepsin B, over-expressed in TNBC. Stable nanostructures were formed by these two polymer prodrug conjugates co-assembly (PPCC). The stimuli-responsiveness of PPCC was confirmed, and the size shrinkage under tumor microenvironment would facilitate the penetration of PPCC into tumor tissue. In vitro experiments revealed the molecular mechanism for the synergistic effect of the combination of DTX and YC-1. Moreover, the systemic side effects were significantly diminished since the biodistribution of PPCC was improved after i.v. administration in vivo. In this context, the co-assembled nano-structural approach could be employed for delivering therapeutic drugs with different mechanisms of action to exert a synergistic anti-tumor effect against solid tumors, including triple-negative breast cancer. STATEMENT OF SIGNIFICANCE.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pró-Fármacos
/
Neoplasias de Mama Triplo Negativas
/
Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
Acta Biomater
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
Reino Unido