Therapeutic Nanocarriers Inhibit Chemotherapy-Induced Breast Cancer Metastasis.
Adv Sci (Weinh)
; 9(33): e2203949, 2022 11.
Article
en En
| MEDLINE
| ID: mdl-36220339
ABSTRACT
Chemotherapy, although effective against primary tumors, may promote metastasis by causing the release of proinflammatory factors from damaged cells. Here, polymeric nanoparticles that deliver chemotherapeutics and scavenge proinflammatory factors simultaneously to inhibit chemotherapy-induced breast cancer metastasis are developed. The cationic nanoparticles can adsorb cell-free nucleic acids (cfNAs) based on charge-charge interaction, which downregulates the expression of Toll-like receptors and then reduces the secretion of inflammatory cytokines. Through in vitro structural optimization, cationic polyamidoamine (PAMAM) dendrimers modified with drug-binding dodecyl groups and diethylethanolamine surface groups (PAMAM-G3-C125 -DEEA20 ) exhibit the most desirable combination of nanoparticle size (≈140 nm), drug loading, cytotoxicity, cfNA binding, and anti-inflammatory activity. In the mouse models of breast cancer metastasis, paclitaxel-loaded nanoparticles reduce serum levels of cfNAs and inflammatory cytokines compared with paclitaxel treatment alone and inhibit both primary tumor growth and tumor metastasis. Additionally, no significant side effects are detected in the serum or major organs. These results provide a strategy to deliver chemotherapeutics to primary tumors while reducing the prometastatic effects of chemotherapy.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Nanopartículas
/
Neoplasias
/
Antineoplásicos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Adv Sci (Weinh)
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos