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.　©　2024　Elsevier　Ltd