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

Abstract

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.

Rapid targeting and imaging of mitochondria via carbon dots using an amino acid-based amphiphile as a carrier

“…However, when they were tagged with the nanospherical dots of the P, it was evident that the energy-dependent endocytic procedure for cell uptake was probable and was highly influenced by the ATP and temperature. 59,60 This was confirmed by treating KB cells with CDTP nanoprobes and these were incubated at 4 °C for 45 min. A drastic fall in emission of the nanoprobes was observed (Fig.…”

Optical Nanomaterials for Advanced Bioimaging Applications

“…( b) Confocal fluorescence images of mitochondrial colocalization by sub-10 nm arginine terminated CdSe-ZnS QD in CHO cell. Adapted with permission from ref . Copyright 2023, American Chemical Society.…”

“…Similarly, TPP-conjugated CdSe-ZnS quantum dots are used to target mitochondria in 8 h . More recently, a <10 nm arginine-terminated quantum dot is designed that can efficiently target mitochondria within 1 h via the nonendocytic pathway …”

“…(i) Mitochondria targeting CdSe-ZnS QD with arginine termination. Adapted with permission from ref . Copyright 2023, American Chemical Society.…”

“…So, the mitochondria targeting probe must include a high cationic charge to electrostatically bind with a negative mitochondrial membrane. In addition, lipophilicity of the probe would offer interactions with the mitochondrial cardiolipin (Figure b). Triphenylphosphonium (TPP) is most commonly used to target mitochondria due to its cationic-lipophilic character that strongly interacts with the mitochondrial membrane .…”