Mitochondrial Targeting Amplifies Photothermal-Chemotherapy Synergy to Combat Paclitaxel-Resistant Breast Cancer

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Mitochondria are key targets for cancer therapy, especially for overcoming drug resistance.
• Developing effective drug delivery systems is crucial for targeted cancer treatment.

Purpose of the Study:

• To design a multistage targeting drug delivery system (FT-lipoAu/PTX) for mitochondria-specific photothermal apoptosis.
• To reverse tumor chemoresistance and enhance chemotherapeutic efficacy.

Main Methods:

• Fabrication of liposomes encapsulating gold nanorods, modified with folic acid (FA) and triphenylphosphonium (TPP).
• Utilized dual modification for multistage targeting of folate receptor-overexpressing breast tumor cells.
• Investigated the effect of near-infrared (NIR) laser irradiation on mitochondria and drug resistance proteins.

Main Results:

• FT-lipoAu/PTX accumulated in mitochondria, triggering photothermal apoptosis via mitochondrial membrane depolarization and cytochrome c release.
• Tumor metabolic reprogramming downregulated drug-resistance protein expression (e.g., P-glycoprotein), increasing intracellular drug retention.
• Demonstrated potent tumor growth suppression and minimal systemic toxicity in a chemoresistant breast tumor model.

Conclusions:

• FT-lipoAu/PTX system effectively leverages mitochondria-targeted phototherapy to overcome chemoresistance.
• This approach offers a robust strategy for enhancing chemotherapy efficacy in resistant tumors.
• The system shows promise for improved breast cancer treatment with reduced side effects.