Inhibition of Mitochondrial Biosynthesis using a “Right‐Side‐Out” Membrane‐Camouflaged Micelle to Facilitate the Therapeutic Effects of Shikonin on Triple‐Negative Breast Cancer
Inhibition of Mitochondrial Biosynthesis using a “Right‐Side‐Out” Membrane‐Camouflaged Micelle to Facilitate the Therapeutic Effects of Shikonin on Triple‐Negative Breast Cancer
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DOI：
10.1002/adhm.202200742
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发表时间：
2022
影响因子：
10
通讯作者：
Yan Chen
中科院分区：
文献类型：
--
作者：
Jianqing Peng;Xiaoxia Hu;Shuangqin Fan;Jia Zhou;Shuang Ren;Runbin Sun;Yi Chen;Xiang-Chun Shen;Yan Chen
The mitochondria represent a potential target for the treatment of triple-negative breast cancer (TNBC) and shikonin (SK) has shown remarkable therapeutic effects on TNBC. Herein, it is found that SK possesses potent inhibitory effects on mitochondrial biogenesis via targeting polymerase gamma (POLG). However, its application is restricted by its poor aqueous solubility and stability, and therefore, a biomimetic micelle to aid with tumor lesion accumulation and mitochondria-targeted delivery of SK is designed. A folic acid (FA) conjugated polyethylene glycol derivative (FA-PEG-FA) is inserted onto the external membranes of red blood cells (FP-RBCm) to prepare a right-side-out RBCm-camouflaged cationic micelle (ThTM/SK@FP-RBCm). Both FP-RBCm coating and a triphenylphosphine (TPP) moiety on the periphery of micelles contribute to tumor lesion distribution, receptor-mediated cellular uptake, and electrostatic attraction-dependent mitochondrial targeting, thereby maximizing inhibitory effects on mitochondrial biosynthesis in TNBC cells. Intravenous administration of ThTM/SK@FP-RBCm leads to profound inhibition of tumor growth and lung metastasis in a TNBC mouse model with no obvious toxicity. This work highlights the mitochondria-targeted delivery of SK using a right-side-out membrane-camouflaged micelle for the inhibition of mitochondrial biogenesis and enhanced therapeutic effects on TNBC.
