Supramolecular Modulation of Tumor Microenvironment through Pillar[5]arene-Based Host-Guest Recognition to Synergize Cancer Immunotherapy.
J Am Chem Soc
; 145(34): 18789-18799, 2023 08 30.
Article
em En
| MEDLINE
| ID: mdl-37535445
ABSTRACT
Despite the tremendous breakthrough of immunotherapy, the low response rate and resistance of immune checkpoint inhibitors (ICIs) toward solid tumors occur frequently. A highly hypoxic tumor microenvironment (TME) provides tumor cells with high concentrations of HIF-1α and polyamines to evade immune cell destruction. Reprogramming of an immunogenic TME has exhibited a brilliant future to boost immunotherapeutic performances. Herein, a supramolecular nanomedicine (TAPP) is developed on the basis of host-guest molecular recognition and metal coordination, showing the capability to remodel the immunosuppressive TME. Tamoxifen (Tmx) and Fe3+ are encapsulated into TAPP to achieve the combination of chemotherapy and chemodynamic therapy (CDT). Tmx directly downregulates HIF-1α, and a pillar[5]arene-based macrocyclic host successfully eliminates polyamines in tumors. Enhanced immunogenic cell death is achieved by Tmx and Fe3+, and the therapeutic efficacy is further synergized by immune checkpoint blockade (ICB) therapy. This supramolecular reprogramming modality encourages cytotoxic T lymphocyte infiltration, achieving pre-eminent immune response and long-term tumor suppression.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Calixarenos
/
Gastrópodes
/
Neoplasias
Limite:
Animals
Idioma:
En
Revista:
J Am Chem Soc
Ano de publicação:
2023
Tipo de documento:
Article