Rapid Mitochondria Targeting by Arginine-Terminated, Sub-10 nm Nanoprobe via Direct Cell Membrane Penetration

Although mitochondria have been identified as a potential therapeutic target for the treatment of various diseases, inefficient drug targeting to mitochondria is a major limitation for related therapeutic applications. In the current approach, drug loaded nanoscale carriers are used for mitochondria targeting via endocytic uptake. However, these approaches show poor therapeutic performance due to inefficient drug delivery to mitochondria. Here, we report a designed nanoprobe that can enter the cell via a nonendocytic approach and label mitochondria within 1 h. The designed nanoprobe is <10 nm in size and terminated with arginine/guanidinium that offers direct membrane penetration followed by mitochondria targeting. We found five specific criteria that need to be adjusted in a nanoscale material for mitochondria targeting via the nonendocytic approach. They include <10 nm size, functionalization with arginine/guanidinium, cationic surface charge, colloidal stability, and low cytotoxicity. The proposed design can be adapted for mitochondria delivery of drugs for efficient therapeutic performance.