Novel Mitochondria-Targeted NIR Cyanine Cy750M-C1 Nanoparticles for Chemotherapy against Triple-Negative Breast...

Area of Science:

• Biomedical Engineering
• Cancer Biology
• Nanotechnology

Background:

• Mitochondrial metabolism is crucial for cancer progression, presenting mitochondria as a therapeutic target.
• Existing mitochondria-targeting agents face challenges with solubility and tumor specificity.
• Novel agents are needed for effective cancer imaging and therapy.

Purpose of the Study:

• To synthesize and evaluate a novel near-infrared (NIR) small-molecule dye, Cy750M-C1, for cancer therapy.
• To develop and assess nanoparticles loaded with Cy750M-C1 (Cy750M-C1-FA-NPs) for improved tumor targeting and efficacy.
• To elucidate the anticancer mechanisms of Cy750M-C1 in triple-negative breast cancer (TNBC) cells.

Main Methods:

• Synthesis and characterization of Cy750M-C1 dye and Cy750M-C1-FA-NPs.
• Evaluation of optical properties, mitochondrial localization, and anticancer activity in vitro.
• In vivo studies to assess tumor targeting, growth inhibition, and mechanistic pathways.

Main Results:

• Cy750M-C1 demonstrated specific mitochondrial targeting in TNBC cells.
• Cy750M-C1-FA-NPs exhibited enhanced tumor targeting and significant in vivo tumor growth inhibition.
• The dye induced reactive oxygen species (ROS) production, inhibited mitochondrial complexes and OXPHOS, depleted ATP, activated AMPK, and promoted mitochondrial fission, leading to apoptosis.

Conclusions:

• Cy750M-C1 is a promising mitochondria-targeting agent with NIR fluorescence imaging capabilities for cancer therapy.
• Cy750M-C1-FA-NPs serve as effective drug delivery carriers for enhanced antitumor efficacy.
• The study provides mechanistic insights into Cy750M-C1-induced cancer cell death via mitochondrial pathways.