BODIPY nanoparticles functionalized with lactose for cancer-targeted and fluorescence imaging-guided photodynamic therapy

A series of four lactose-modified BODIPY photosensitizers (PSs) with different substituents (-I, -H, -OCH 3 , and -NO 2 ) in the para -phenyl moiety attached to the meso -position of the BODIPY core were synthesized; the photophysical properties and photodynamic anticancer activities of these sensitizers were investigated, focusing on the electronic properties of the different substituent groups. Compared to parent BODIPY H , iodine substitution (BODIPY I ) enhanced the intersystem crossing (ISC) to produce singlet oxygen ( 1 O 2 ) due to the heavy atom effect, and maintained a high fluorescence quantum yield (Φ F ) of 0.45. Substitution with the electron-donating methoxy group (BODIPY OMe) results in a significant perturbation of occupied frontier molecular orbitals and consequently achieves higher 1 O 2 generation capability with a high Φ F of 0.49, while substitution with the electron-withdrawing nitro group (BODIPY NO2 ) led a perturbation of unoccupied frontier molecular orbitals and induces a forbidden dark S 1 state, which is negative for both fluorescence and 1 O 2 generation efficiencies. The BODIPY PSs formed water-soluble nanoparticles (NPs) functionalized with lactose as liver cancer-targeting ligands. BODIPY I and OMe NPs showed good fluorescence imaging and PDT activity against various tumor cells (HeLa and Huh-7 cells). Collectively, the BODIPY NPs demonstrated high 1 O 2 generation capability and Φ F may create a new opportunity to develop useful imaging-guided PDT agents for tumor cells.