Designed Nanodrugs\nfor Ultrasonic Removal of Toxic\nPolyglutamine Aggregates from Neuron Cells

Clearing of toxic polyglutamine aggregates from neuronal\ncells\nis crucial for ameliorating Huntington’s disease. However,\nsuch clearance is challenging, requiring the targeting of affected\nneuron cells in the brain, followed by the removal of polyglutamine\nfrom cells. Here we report a designed nanodrug that can be used for\nthe ultrasound-based removal of toxic polyglutamine aggregates from\nneuron cells. The nanodrug is composed of a sonosensitizer molecule,\nchlorin e6- or protoporphyrin IX-loaded polymer micelle of 20–30\nnm in size that rapidly delivers the sonosensitizer into the cell\nnucleus. Ultrasound exposure of these cells generates singlet oxygen\nin the nucleus/perinuclear region that induces strong autophagic flux\nand clears toxic polyglutamine aggregates from cells. It has been\ndemonstrated that the nanodrug and ultrasound treatment can enhance\nthe cell survival against polyglutamine aggregates by 4 times. This\nresult suggests that the nanodrug can be designed for focused ultrasound-based\nwireless treatment of various neurodegenerative diseases.