Details

Autor(en) / Beteiligte

• Shen, Wenhao
• Liu, Teng
• Pei, Pei
• Li, Junmei
• Yang, Sai
• Zhang, Yanxiang
• Zhou, Hailin
• Hu, Lin
• Yang, Kai

Titel

Metabolic Homeostasis‐Regulated Nanoparticles for Antibody‐Independent Cancer Radio‐Immunotherapy

Ist Teil von

• Advanced materials (Weinheim), 2022-12, Vol.34 (51), p.e2207343-n/a

Ort / Verlag

Germany: Wiley Subscription Services, Inc

Erscheinungsjahr

2022

Quelle

Wiley InterScience Journals

Beschreibungen/Notizen

• The special metabolic traits of cancer cells and tumor‐associated macrophages (TAMs) in the tumor microenvironment (TME) are promising targets for developing novel cancer therapy strategies, especially the glycolysis and mitochondrial energy metabolism. However, therapies targeting a singular metabolic pathway are always counteracted by the metabolic reprogramming of cancer, resulting in unsatisfactory therapeutic effect. Herein, this work employs poly(ethylene glycol)‐coated (PEGylated) liposomes as the drug delivery system for both mannose and levamisole hydrochloride to simultaneously inhibit glycolysis and restrain mitochondrial energy metabolism and thus inhibit tumor growth. In combination with radiotherapy, the liposomes can not only modulate the immunosuppressive TME by cellular metabolism regulation to achieve potent therapeutic effect for local tumors, but also suppress the M2 macrophage proliferation triggered by X‐ray irradiation and thus enhance the immune response to inhibit metastatic lesions. In brief, this work provides a new therapeutic strategy targeting the special metabolic traits of cancer cells and immunosuppressive TAMs to enhance the abscopal effect of radiotherapy for cancer. In order to modulate the immunosuppressive tumor microenvironment aggravated by X‐ray irradiation, a liposome loaded with mannose and levamisole (M/LM‐Lipo) is developed for cellular metabolism regulation and macrophage polarization. The M/LM‐Lipo orchestrates radio‐immunotherapy by the simultaneous modulation of glucose and mitochondrial metabolic pathways in both cancer cells and macrophages, achieving systematic antitumor immune response for effective tumor ablation and metastasis elimination.