Light-responsive α-TOS liposomal nanocarriers Co-delivering TiO2 and doxorubicin for the treatment of breast cancer

Doxorubicin (DOX) is limited by its clinical toxicity as a breast cancer therapy. Traditional liposomal formulations improve the tumor delivery of DOX but suffer from inadequate controlled release and low encapsulation efficiency of DOX. To address these, we developed a photo-responsive liposomal formulation DTTPL by co-encapsulating DOX and TiO 2 nanostructures (TiO 2 ) within D-α-tocopheryl succinate (α-TOS)-PEG liposomes. DTTPL successfully facilitated the release of DOX through the light-sensitive catalysis mechanism of TiO 2 , exhibiting 4.6 times greater cytotoxicity against MCF-7 cells compared to free DOX. Transcriptional analysis revealed synergistic DOX/DTTPL dysregulation of key genes (Brca1, Bcl-2, Bax, Caspase-3), aligning with cytotoxicity.   Eventually, light-triggered DOX/DTTPL formulation resulted in 70.09% of tumor growth inhibition (TGI) in mice with no significant organ toxicity. This photo-responsive nanoformulation enables efficient controlled release of DOX, offering an alternative strategy for small molecule delivery to treat triple negative breast cancer.