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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\u2010targeted delivery of SK is designed. A folic acid (FA) conjugated polyethylene glycol derivative (FA\u2010PEG\u2010FA) is inserted onto the external membranes of red blood cells (FP\u2010RBCm) to prepare a \u201cright\u2010side\u2010out\u201d RBCm\u2010camouflaged cationic micelle (ThTM\/SK@FP\u2010RBCm). Both FP\u2010RBCm coating and a triphenylphosphine (TPP) moiety on the periphery of micelles contribute to tumor lesion distribution, receptor\u2010mediated cellular uptake, and electrostatic attraction\u2010dependent mitochondrial targeting, thereby maximizing inhibitory effects on mitochondrial biosynthesis in TNBC cells. Intravenous administration of ThTM\/SK@FP\u2010RBCm leads to profound inhibition of tumor growth and lung metastasis in a TNBC mouse model with no obvious toxicity. This work highlights the mitochondria\u2010targeted delivery of SK using a \u201cright\u2010side\u2010out\u201d membrane\u2010camouflaged micelle for the inhibition of mitochondrial biogenesis and enhanced therapeutic effects on TNBC.<\/jats:p>","DOI":"10.1002\/adhm.202200742","type":"journal-article","created":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T06:35:33Z","timestamp":1657607733000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Inhibition of Mitochondrial Biosynthesis Using a \u201cRight\u2010Side\u2010Out\u201d Membrane\u2010Camouflaged Micelle to Facilitate the Therapeutic Effects of Shikonin on Triple\u2010Negative Breast Cancer"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3351-7124","authenticated-orcid":false,"given":"Jianqing","family":"Peng","sequence":"first","affiliation":[{"name":"The High Efficacy Application of Natural Medicinal Resources 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