A Gene-Editable Palladium-Based Bioorthogonal Nanoplatform Facilitates Macrophage Phagocytosis for Tumor Therapy.
Journal
Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543
Informations de publication
Date de publication:
11 Dec 2023
11 Dec 2023
Historique:
received:
19
09
2023
medline:
7
12
2023
pubmed:
27
10
2023
entrez:
26
10
2023
Statut:
ppublish
Résumé
Macrophage phagocytosis of tumor cells has emerged as an attractive strategy for tumor therapy. Nevertheless, immunosuppressive M2 macrophages in the tumor microenvironment and the high expression of anti-phagocytic signals from tumor cells impede therapeutic efficacy. To address these issues and improve the management of malignant tumors, in this study we developed a gene-editable palladium-based bioorthogonal nanoplatform, consisting of CRISPR/Cas9 gene editing system-linked Pd nanoclusters, and a hyaluronic acid surface layer (HBPdC). This HBPdC nanoplatform exhibited satisfactory tumor-targeting efficiency and triggered Fenton-like reactions in the tumor microenvironment to generate reactive oxygen species for chemodynamic therapy and macrophage M1 polarization, which directly eliminated tumor cells, and stimulated the antitumor response of macrophages. HBPdC could reprogram tumor cells through gene editing to reduce the expression of CD47 and adipocyte plasma membrane-associated protein, thereby promoting their recognition and phagocytosis by macrophages. Moreover, HBPdC induced the activation of sequestered prodrugs via bioorthogonal catalysis, enabling chemotherapy and thereby enhancing tumor cell death. Importantly, the Pd nanoclusters of HBPdC were sufficiently cleared through basic metabolic pathways, confirming their biocompatibility and biosafety. Therefore, by promoting macrophage phagocytosis, the HBPdC system developed herein represents a highly promising antitumor toolset for cancer therapy applications.
Identifiants
pubmed: 37884479
doi: 10.1002/anie.202313968
doi:
Substances chimiques
Palladium
5TWQ1V240M
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e202313968Subventions
Organisme : National Key R&D Program of China
ID : 2019YFA0709200
Organisme : National Natural Science Foundation of China
ID : 21874066
Organisme : National Natural Science Foundation of China
ID : 22301136
Organisme : Key Research and Development Program of Jiangsu Province
ID : BE2021373
Organisme : Natural Science Foundation of Jiangsu Province
ID : BK20200336
Organisme : Natural Science Foundation of Jiangsu Province
ID : BK20230942
Organisme : Program for Innovative Talents and Entrepreneur in Jiangsu
Organisme : State Key Laboratory of Analytical Chemistry for Life Science
ID : 5431ZZXM2304
Informations de copyright
© 2023 Wiley-VCH GmbH.
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