MOF-derived intelligent arenobufagin nanocomposites with glucose metabolism inhibition for enhanced bioenergetic therapy and integrated photothermal-chemodynamic-chemotherapy.

Publisher: BioMed Central Country of Publication: England NLM ID: 101152208 Publication Model: Electronic Cited Medium: Internet ISSN: 1477-3155 (Electronic) Linking ISSN: 14773155 NLM ISO Abbreviation: J Nanobiotechnology Subsets: MEDLINE

Original Publication: London : BioMed Central, 2003-

Glucose*/metabolism ; Bufanolides*/chemistry ; Bufanolides*/pharmacology ; Nanocomposites*/chemistry ; Photothermal Therapy*/methods ; Metal-Organic Frameworks*/chemistry; Energy Metabolism/drug effects ; Apoptosis/drug effects ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/chemistry ; Animals ; Humans ; Mice ; Cell Line, Tumor ; Mice, Inbred BALB C ; Mice, Nude

Bioenergetic therapy based on tumor glucose metabolism is emerging as a promising therapeutic modality. To overcome the poor bioavailability and toxicity of arenobufagin (ArBu), a MOF-derived intelligent nanosystem, ZIAMH, was designed to facilitate energy deprivation by simultaneous interventions of glycolysis, OXPHOS and TCA cycle. Herein, zeolitic imidazolate framework-8 was loaded with ArBu and indocyanine green, encapsulated within metal-phenolic networks for chemodynamic therapy and hyaluronic acid modification for tumor targeting. ZIAMH nanoparticles can release ArBu in the tumor microenvironment for chemtherapy, and ICG enables photothermal therapy under near-infrared laser irradiation. In vitro and in vivo mechanism studies revealed that the ZIAMH nanoplatform downregulated glucose metabolism related genes, resulting in the reduction of energy substances and metabolites in tumors. Additionally, it significantly promoted cell apoptosis by upregulating pro-apoptotic proteins such as Bax, Bax/Bcl-2, cytochrome C. Animal studies have shown that the tumor inhibition efficiency of ZIAMH nanomedicines was three fold higher than that of free drugs. Therefore, this study provides a new strategy for glucose metabolism-mediated bioenergetic therapy and PTT/CDT/CT combined therapy for tumors.
(© 2025. The Author(s).)

Declarations. Ethics approval and consent to participate: All animal experiment procedures were approved by the Institutional Animal Care and Use Committee of the Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, and followed the Guide for the Care and Use of Laboratory Animals. Consent for publication: All the authors agree to the publication of the article. Competing interests: The authors declare no competing interests.

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ZZ17-YQ-015 Fundamental Research Funds for the Central Public Welfare Research Institutes of China; ZZ15-YQ-032 Fundamental Research Funds for the Central Public Welfare Research Institutes of China; CI2023C020YL Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences

Keywords: Arenobufagin; Bioenergetic therapy; Glycolysis; Integrated photothermal-chemodynamic-chemotherapy; Nanomedicine; Oxidative phosphorylation; Tricarboxylic acid cycle

IY9XDZ35W2 (Glucose)
0 (Bufanolides)
0 (Metal-Organic Frameworks)
0 (Antineoplastic Agents)

Date Created: 20250117 Date Completed: 20250501 Latest Revision: 20250522

20260130

PMC11740360

10.1186/s12951-024-03084-1

39819479