Details

Autor(en) / Beteiligte

• Duan, Qiu‐Yi
• Zhu, Ya‐Xuan
• Shan, Bai‐Hui
• Guo, Yuxin
• Xu, Ke‐Fei
• Jia, Hao‐Ran
• Wu, Fu‐Gen

Titel

Reallocating Cell Respiration Substrates for Cancer Therapy Using a Metabolism Regulator with an Intermembrane‐Translocatable Accessory

Ist Teil von

• Advanced functional materials, 2023-06, Vol.33 (23), p.n/a

Ort / Verlag

Hoboken: Wiley Subscription Services, Inc

Erscheinungsjahr

2023

Quelle

Wiley-Blackwell Full Collection

Beschreibungen/Notizen

• One hallmark of cancer cells is aberrant glucose metabolism. By desperately consuming glucose, cancer cells grow quickly and form a hypoxic core in the tumor, which severely limits the efficacy of oxygen‐dependent therapeutic strategies. Herein, a cell metabolism regulation strategy is adopted to reallocate cell respiration substrates for fueling the processes for cancer therapy by constructing a metabolism nanoregulator (denoted as ATO/GOx PLP). To be specific, a protoporphyrin IX (PpIX, the intermembrane‐translocatable accessory)‐doped liposome is employed for direct intracellular delivery of GOx and atovaquone (ATO, a mitochondrial complex III inhibitor). The PpIX‐doped liposome can efficiently avoid the cargo leakage in blood circulation. Benefiting from the translocation of PpIX from the liposome to the cancer cell membrane, ATO and GOx can be rapidly released upon encountering the plasma membrane and internalized by the cancer cell. By inhibiting mitochondrial oxidative phosphorylation and regulating mitochondrial function, ATO reduces both oxygen consumption and glucose metabolism, sparing more substrates for GOx to kill cancer cells. As a result, ATO/GOx PLP presents outstanding anticancer efficacies both in vitro and in vivo. In addition, the ATO/GOx PLP exhibits excellent biosafety, showing its clinical translation potential. Overall, this study provides a new approach to achieve efficacious metabolism regulation‐based cancer therapy. A cell metabolism regulation strategy to reallocate the cell respiration substrates for fueling the glucose oxidase (GOx) catalysis process for cancer therapy is developed by constructing a metabolism nanoregulator. More importantly, it is also demonstrated that the carrier of the nanoregulator, the protoporphyrin IX (PpIX)‐doped liposome, can directly and responsively release the encapsulated cargoes via an interesting PpIX translocation process.