Over 10 Times Enhanced Therapeutic Performance of Sonosensitizers/Photosensitizers via Nanocarrier-Based Mitochondria Targeting

Abstract Although mitochondria targeting is crucial for enhanced therapeutic performance of various diseases, such delivery is challenging, which requires crossing of the cell membrane barrier followed by intracellular trafficking to mitochondria. Recent works show that direct membrane penetrating nanocarriers can offer efficient cell nucleus/mitochondria delivery, bypassing the endosomal/lysosomal trafficking. Here, we show that nanocarrier-based mitochondria delivery of a sonosensitizer/photosensitizer can enhance the therapeutic performance by >10 times. The sonosensitizer/photosensitizer is delivered into mitochondria via a nanocarrier-based nonendocytic approach. Next, cells are exposed with ultrasound/light for generating reactive oxygen species at/near mitochondria that induce oxidative stress and cytotoxicity. We observe that mitochondria targeting has enhanced the therapeutic performance by 10−20 times as compared to the conventional carrier-based endocytic delivery-based therapy of the sonosensitizer/photosensitizer. This developed approach can be adapted for mitochondria-targeted advanced therapeutic applications. Supporting Information