BODIPY Nanoparticles Functionalized With Lactose for Cancer-Targeted and Fluorescence Imaging-guided Photodynamic Therapy

Abstract

Abstract 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. 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 45.3%. Substitution with the electron-donating group (-OCH 3 ) (BODIPY OMe) resulted in a high 1 O 2 generation capability and a Φ F of 49.2% while substitution with the electron-withdrawing group (-NO 2 ) led to the PeT process. Thus, instead of assisting ISC as typically expected, this BODIPY PS induced non-radiative charge recombination, prohibiting both fluorescence emission and 1 O 2 generation. 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.