A dual-sensitive nanoparticle-mediated deepening synergistic therapy strategy involving DNA damage and ICD stimuli to treat triple-negative breast cancer.
Biomater Sci
; 11(18): 6325-6341, 2023 Sep 12.
Article
en En
| MEDLINE
| ID: mdl-37555273
ABSTRACT
Triple-negative breast cancer (TNBC) is one of the most aggressive cancers with an immunosuppressive microenvironment, and achieving a satisfactory effect from monotherapies, such as chemotherapy, photodynamic therapy (PDT) or immunotherapy, remains difficult. To solve this puzzle, a deepening synergistic therapy strategy of DNA damage and immunogenic cell death (ICD) stimuli was proposed. We engineered a doxorubicin (DOX) and 4-(hydroxymethyl) phenylboronic acid pinacol ester (PBAP) prodrug polymer, and encapsulated chlorin e6 (Ce6) to obtain the hyaluronidase (HAase) and H2O2 dual-sensitive responsive nanoparticles (Ce6/HDP NPs). The NPs displayed efficient intratumoral accumulation and cellular internalization properties due to the active targeting of the hyaluronic acid (HA). The dual DNA damage of the chemotherapy and ROS production directly caused tumor cell apoptosis. The strong ICD stimuli, which were induced by ROS production and GSH depletion, generated an amplified immunogenicity to activate tumor immunotherapy in vivo. In this manner, the NPs could significantly inhibit primary tumor, abscopal tumor, pulmonary metastasis and recurrent tumor in a subcutaneous 4T1 tumor model, with effective biosafety. This study has provided a promising deepening synergistic therapy strategy against TNBC.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fotoquimioterapia
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Porfirinas
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Nanopartículas
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Neoplasias de la Mama Triple Negativas
Tipo de estudio:
Diagnostic_studies
Límite:
Humans
Idioma:
En
Revista:
Biomater Sci
Año:
2023
Tipo del documento:
Article