Abstract
Clearing of toxic polyglutamine aggregates from neuronal cells is crucial for ameliorating Huntington's disease. However, such clearance is challenging, requiring the targeting of affected neuron cells in the brain, followed by the removal of polyglutamine from cells. Here we report a designed nanodrug that can be used for the ultrasound-based removal of toxic polyglutamine aggregates from neuron cells. The nanodrug is composed of a sonosensitizer molecule, chlorin e6- or protoporphyrin IX-loaded polymer micelle of 20-30 nm in size that rapidly delivers the sonosensitizer into the cell nucleus. Ultrasound exposure of these cells generates singlet oxygen in the nucleus/perinuclear region that induces strong autophagic flux and clears toxic polyglutamine aggregates from cells. It has been demonstrated that the nanodrug and ultrasound treatment can enhance the cell survival against polyglutamine aggregates by 4 times. This result suggests that the nanodrug can be designed for focused ultrasound-based wireless treatment of various neurodegenerative diseases.
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