Tumor cell-derived extracellular vesicles for breast cancer specific delivery of therapeutic P53

Breast cancer has consistently had the highest incidence among women in the world. Tumor cell-derived extracellular vesicles (EV) have been leveraged as drug carriers for cancer treatment. Herein, we developed an efficient theranostic platform for breast cancer-specific delivery of lipophilic triphenylphosphonium (TPP)modified therapeutic recombinant P53 proteins (TPP/P53) by breast cancer cell-derived EVs. We observed that the EVs were routinely captured by their patent cells, so when, TPP/P53 was loaded into the EVs (TPP/ P53@EVs), TPP/P53 was targeted to the mitochondria of breast cancer cells, where it caused signal amplification and induced the death of breast cancer cells. Our findings demonstrated that the TPP/P53@EVs showed good tumor-targeting capability and efficiently destroyed the tumor tissues without any obvious toxicity in vivo. Therefore, our TPP/P53@EVs might provide a drug-free strategy for future applications in breast cancer therapy.

Automated summary

Breast cancer, with the highest incidence among women worldwide, can be targeted and treated efficiently using a theranostic platform that delivers therapeutic proteins through extracellular vesicles (EVs) derived from breast cancer cells. This study demonstrates that EVs loaded with lipophilic triphenylphosphonium (TPP)-modified P53 proteins specifically target mitochondria in breast cancer cells, leading to amplified signals and cell death. The findings suggest that this drug-free strategy using TPP/P53@EVs has potential for future breast cancer therapy.