A Paclitaxel Prodrug with Copper Depletion for Combined Therapy toward Triple-Negative Breast Cancer

Area of Science:

• Nanomedicine
• Cancer Therapy
• Drug Delivery Systems

Background:

• Copper homeostasis is crucial for treating cancer and neurodegenerative diseases.
• Developing targeted drug delivery systems can improve therapeutic efficacy and reduce side effects.

Purpose of the Study:

• To synthesize a redox-responsive paclitaxel (PTX) prodrug for targeted cancer therapy.
• To investigate the combined effects of chemotherapy and copper depletion in triple-negative breast cancer (TNBC).

Main Methods:

• Conjugation of PTX with a copper chelator via a disulfide bond to create a prodrug (PSPA).
• Self-assembly of PSPA with distearoyl phosphoethanolamine-PEG2000 to form nanoparticles (PSPA NPs).
• Evaluation of PSPA NPs' cellular uptake, drug release, copper chelation, and therapeutic efficacy in TNBC models.

Main Results:

• PSPA NPs demonstrated specific copper chelation and efficient PTX release in response to intracellular redox conditions.
• Copper depletion by the chelator enhanced oxidative stress and induced cancer cell death.
• Combined chemotherapy and copper depletion therapy significantly improved therapeutic outcomes in TNBC with minimal systemic toxicity.

Conclusions:

• The developed redox-responsive PTX prodrug nanoparticles offer a promising strategy for enhanced cancer treatment.
• Combining chemotherapy with copper depletion therapy presents a novel approach for combating malignant tumors like TNBC.
• This study provides insights into integrating metabolic regulation with chemotherapy for improved cancer therapy.