N-bridging tetra-substituted zinc(II) phthalocyanines with Q-band absorption up to 780 nm and eminent photosensitizing activities for photodynamic therapy

Abstract

With a view to developing highly efficient photosensitizers for photodynamic therapy, herein, we prepared a series of tetra-substituted zinc(II) phthalocyanine analogues (ZPOP, ZPSP, ZPNP, and ZPNPM) modified with O-, S-, and N-bridging substituents, respectively. Compared to O- and S-bridging analogues, the N-bridging phthalocyanines showed eminent red-shifted Q band absorption (750–780 nm) and excellent reactive oxygen species (ROS) generation ability (ΦΔ = 0.90–0.97), due to the HOMO destabilization, as well as the smaller ΔEST. To improve the hydrophility and biocompatibility, we further prepared two N-bridging zinc(II) phthalocyanines (ZPN1 and ZPN2) modified with morpholine and N,N-dimethylamine moieties, respectively, along with their quaternized counterparts (QZPN1 and QZPN2). These compounds exhibited NIR-absorbing Q bands at 774–777 nm and efficient ROS generation ability in aqueous solutions, especially formulated with 1 % Cremophor EL (Cel). In vitro studies indicated that ZPN2 exhibited the highest photodynamic activity against HepG2 cells (IC50 = 0.44 ± 0.02 μM), because of superior cellular uptake and moderate ROS generation ability. Moreover, ZPN2 could selectively accumulate and retain in tumor tissue of H22 tumor-bearing mice. The work presents a new strategy for the development of NIR-absorbing photosensitizers.