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

Althoughmitochondria have been identified as a potential therapeutictarget for the treatment of various diseases, inefficient drug targetingto mitochondria is a major limitation for related therapeutic applications.In the current approach, drug loaded nanoscale carriers are used formitochondria targeting via endocytic uptake. However, these approachesshow poor therapeutic performance due to inefficient drug deliveryto mitochondria. Here, we report a designed nanoprobe that can enterthe cell via a nonendocytic approach and label mitochondria within1 h. The designed nanoprobe is <10 nm in size and terminated witharginine/guanidinium that offers direct membrane penetration followedby mitochondria targeting. We found five specific criteria that needto be adjusted in a nanoscale material for mitochondria targetingvia the nonendocytic approach. They include <10 nm size, functionalizationwith arginine/guanidinium, cationic surface charge, colloidal stability,and low cytotoxicity. The proposed design can be adapted for mitochondriadelivery of drugs for efficient therapeutic performance.

Automated summary

Although mitochondria have been recognized as a potential therapeutic target, inefficient drug targeting limits their therapeutic applications. In this study, a designed nanoprobe with arginine/guanidinium terminated surface was developed for nonendocytic mitochondria targeting. The nanoprobe demonstrated efficient penetration and specific labeling of mitochondria within 1 hour, providing a promising strategy for mitochondria delivery of drugs.