Anticancer Tetranuclear Cu(I) Complex Catalyzes a Click Reaction to Synthesize a Chemotherapeutic Agent in situ to Achieve Targeted Dual-Agent Combination Therapy for Cancer.

Publisher: Wiley-VCH Country of Publication: Germany NLM ID: 0370543 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1521-3773 (Electronic) Linking ISSN: 14337851 NLM ISO Abbreviation: Angew Chem Int Ed Engl Subsets: MEDLINE

Publication: <2004-> : Weinheim : Wiley-VCH
Original Publication: Weinheim/Bergstr. : New York, : Verlag Chemie ; Academic Press, c1962-

Copper*/chemistry ; Click Chemistry* ; Antineoplastic Agents*/chemistry ; Antineoplastic Agents*/pharmacology ; Antineoplastic Agents*/chemical synthesis ; Coordination Complexes*/chemistry ; Coordination Complexes*/pharmacology ; Coordination Complexes*/chemical synthesis ; Coordination Complexes*/therapeutic use; Humans ; Catalysis ; Animals ; Cell Line, Tumor ; Neoplasms/drug therapy ; Drug Screening Assays, Antitumor ; Mice ; Alkynes/chemistry ; Cycloaddition Reaction ; Cell Proliferation/drug effects ; Apoferritins/chemistry ; Azides/chemistry ; Nanoparticles/chemistry

To develop next-generation metal-based drugs and dual-drug combination therapy for cancer, we proposed to develop a copper (Cu) complex that exerts anticancer function by integrating chemotherapy, immunotherapy and catalyzes a click reaction for the in situ synthesis of a chemotherapeutic agent, thereby achieving targeted dual-agent combination therapy. We designed and synthesized a tetranuclear Cu(I) complex (Cu4) with remarkable cytotoxicity and notable catalytic ability for the in situ synthesis of a chemotherapeutic agent via Cu(I)-catalyzed azide-alkyne 1,3-cycloaddition (CuAAC). We also constructed an apoferritin (AFt)-Cu4 nanoparticles (NPs) delivery system. Aft-Cu4 NPs not only showed an enhanced performance of tumor growth inhibition, but also improved the targeting ability and reduced the systemic toxicity of Cu4 in vivo. Importantly, the anticancer effect was enhanced by combining the Aft-Cu4 NPs with the resveratrol analogue obtained from the CuAAC reaction in situ. Finally, we revealed the anticancer mechanism of the Cu4/Aft-Cu4 NPs, which involves both cuproptosis and cuproptosis-induced systemic immune response.
(© 2024 Wiley-VCH GmbH.)

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2022GXNSFGA035003 Natural Science Foundation of Guangxi; 22077021 Natural Science Foundation of China

Keywords: CuAAC; anticancer; combination therapy; cuproptosis; immune response

789U1901C5 (Copper)
0 (Antineoplastic Agents)
0 (Coordination Complexes)
0 (Alkynes)
9013-31-4 (Apoferritins)
0 (Azides)

Date Created: 20240919 Date Completed: 20241209 Latest Revision: 20241209

20241210

10.1002/anie.202411846

39295439