Modulation of macrophage polarity with carboxymethyl chitin gated hollow mesoporous silica nanoparticles for elevating anti-tumor chemotherapy.
Int J Biol Macromol
; 261(Pt 2): 129761, 2024 Mar.
Article
em En
| MEDLINE
| ID: mdl-38290634
ABSTRACT
The weak immunity of tumors after chemotherapy could cause tumor metastasis and progression. Therefore, to overcome the dilemma of obvious immune deficiency caused by chemotherapy, a nanosystem (N-IL-12/DOX/α-TOS) consisted of thioketal (TK) bonds linked-hollow mesoporous silica nanoparticles (HMSNs) coated with carboxymethyl chitin (CMCH) by electrostatic interaction, and surface-functionalized glucose-regulated protein 78 binding peptide was prepared for loading doxorubicin (DOX), IL-12 and α-tocopheryl succinate (α-TOS). N-IL-12/DOX/α-TOS displayed a mean size of 275 nm after encapsulated DOX, IL-12 and α-TOS with loading contents of 2.04 × 10-4, 4.01 × 10-2 and 7.12 × 10-2, respectively. The drug-free nanoparticles (NPs) showed good biocompatibility to both 4 T1 cells and RAW264.7 macrophages. N-IL-12/DOX/α-TOS could achieve localized release of IL-12, DOX and α-TOS by pH and H2O2 trigger in the tumor microenvironment (TME). Moreover, the combined therapy by N-IL-12/DOX/α-TOS remarkably elevated the anti-tumor therapeutic efficacy, enhanced immune responses via promoting tumor-associated macrophage (TAM) polarization into tumoricidal M1 phenotypes, and decreased lung metastasis with reduced side effects. N-IL-12/DOX/α-TOS exhibited as a promising strategy for combining chemotherapy and local macrophage modulation-immunotherapy for anti-tumor therapy.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Nanopartículas
/
Neoplasias
Limite:
Humans
Idioma:
En
Revista:
Int J Biol Macromol
Ano de publicação:
2024
Tipo de documento:
Article