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The mitochondrion is an important sub-cellular organelle responsible for the cellular energetic source and processes. Owing to its unique sensitivity to heat and reactive oxygen species, theĀ mitochondrion is an appropriate target for photothermal and photodynamic treatment for cancer. However, targeted delivery of therapeutics to mitochondria remains a great challenge due to their location in the sub-cellular compartment and complexity of the intracellular environment. Herein, we report a class of the mitochondrion-targeted liposomal delivery platform consisting of a guanidinium-based dendritic peptide moiety mimicking mitochondrion protein transmembrane signaling to exert mitochondrion-targeted delivery with pH sensitive and charge-reversible functions to enhance tumor accumulation and cell penetration. Compared to the current triphenylphosphonium (TPP)-based mitochondrion targeting system, this dendritic lipopeptide (DLP) liposomal delivery platform exhibits about 3.7-fold higher mitochondrion-targeted delivery efficacy. Complete tumor eradication is demonstrated in mice bearing 4T1 mammary tumors after combined photothermal and photodynamic therapies delivered by the reported DLP platform.


Lei Jiang, Sensen Zhou, Xiaoke Zhang, Cheng Li, Shilu Ji, Hui Mao, Xiqun Jiang. Mitochondrion-specific dendritic lipopeptide liposomes for targeted sub-cellular delivery. Nature communications. 2021 Apr 22;12(1):2390

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PMID: 33888699

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