Abstract

Lysosome-targeting therapy has emerged as a promising strategy for combating drug-resistant tumors. However, the synthesis of nanodrugs to achieve efficient lysosome targeting remains a challenging task. In this study, a nanoparticle DSPE@TPA-FBPA-SiPc was developed for lysosome targeting therapy. The nanoparticle was prepared by loading 2-[4-(diphenylamino)-1-diphenicacid-1-carbobenzoxy-4-(1,1,1,3,3,3-hexafluoropropane-4-phenoxy) silicon phthalocyanine (TPA-FBPA-SiPc) into 1,2-distearoyl-sn‑glycero-3-phosphoethanolamine-N-[succinyl(polyethyleneglycol)-2000] (DSPE). DSPE@TPA-FBPA-SiPc demonstrated remarkable capabilities such as two-color imaging, lysosome targeting and in vitro photodynamic therapy functions. The results revealed that DSPE@TPA-FBPA-SiPc efficiently accumulated in lysosomes, leading to generation of a high amount of reactive oxygen species upon irradiation. This induced apoptosis in MCF-7 cells by disrupting lysosomal function. Consequently, DSPE@TPA-FBPA-SiPc holds great potential as a photosensitizer for photodynamic therapy, utilizing the lysosomal-mediated cell death pathway.

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