Boosting Tumor Accumulation of Phthalocyanine through Sialylation Engineering for Superior Cancer Phototherapy

Phthalocyanines (Pcs) are widely developed in cancer phototherapy due to their definite chemical structure and tunable photosensitivity. However, their in vivo application is hampered by low water solubility and non-specific biodistribution. Here,a strategy of sialylation-modulation is developed for the first time to highly improve the bioavailability of Pcs. The sialylated Pcs (ZnPc-4SA) not only has good hydrophilicity, but also can self-assemble into nanoparticles (ZnPc-4SA NPs). These nanoformulations retain the excellent photophysical properties of Pcs, which in turn reflects excellent optoacoustic and phototherapeutic properties. Importantly, ZnPc-4SA NPs exhibit boosted tumor accumulation due to the passive targeting and sialic acid-mediated E-selectin targeting. Besides, the phototoxicity of ZnPc-4SA NPs can effectively trigger cell apoptosis and tumor elimination upon laser irradiation. Therefore, sialylation engineering strategy provides a new option for hydrophobic drugs modification with enhanced tumor theranostics.