Pentalysine β‐Carbonylphthalocyanine Zinc: An Effective Tumor‐Targeting Photosensitizer for Photodynamic Therapy

Abstract

Unsymmetrical phthalocyanine derivatives have been widely studied as photosensitizers for photodynamic therapy (PDT), targeting various tumor types. However, the preparation of unsymmetrical phthalocyanines is always a challenge due to the presence of many possible structural isomers. Herein we report a new unsymmetrical zinc phthalocyanine, pentalysine β-carbonylphthalocyanine zinc (ZnPc-(Lys) 5 ), that was prepared in large quantity and high purity. This is a water-soluble cationic photosensitizer and maintains a high quantum yield of singlet oxygen generation similar to that of unsubstituted zinc phthalocyanine (ZnPc). Compared with anionic ZnPc counterparts, ZnPc-(Lys) 5 shows a higher level cellular uptake and 20-fold higher phototoxicity toward tumor cells. Pharmacokinetics and PDT studies of ZnPc-(Lys) 5 in S180 tumor-bearing mice showed a high ratio of tumor versus skin retention and significant tumor inhibition. This new molecular framework will allow synthetic diversity in the number of lysine residues incorporated and will facilitate future QSAR studies.

Photodynamic antimicrobial chemotherapy using zinc phthalocyanine derivatives in treatment of bacterial skin infection

“…ZnPc-ðLysÞ 5 , a phthalocyanine derivative with five positive charges, prepared as a high purity single isomer, was previously reported 13 as an effective photosensitizer with high activity in both cultured tumor cells and experimental animal tumors. 14 To further investigate the photodynamic inactivation of ZnPc-ðLysÞ 5 on microorganisms involved in skin bacterial infections, we evaluated the antibacterial efficacy of ZnPc-ðLysÞ 5 in vitro and in vivo using the key pathogenic factors P. acnes and S. aureus. This study may provide a safe and effective approach for the treatment of bacterial skin infections.…”

A Novel Tumor Targeting Drug Carrier for Optical Imaging and Therapy

“…We further measured the fluorescence spectra of ATF-HSA:CPZ. Surprisingly, the fluorescence intensity of CPZ in ATF-HSA:CPZ in saline was ~100-fold higher than the control PS, ZnPc-(Lys) 5 36, which is a water soluble CPZ derivative (Figure 3B). The absolute fluorescence quantum yield of ATF-HSA:CPZ was 0.8%.…”

Silicon Phthalocyanines Axially Disubstituted with Erlotinib toward Small‐Molecular‐Target‐Based Photodynamic Therapy

“…All conjugates essentially had no dark cytotoxicity,a nd exhibited significantly highp hoto-cytotoxicityu pon low-dose light illumination (670 nm, 1.5 Jcm À2 , 25 mW cm À2 )w hich is usuallyu sed in phthalocyanine-based PDT. [21,22,[45][46][47] Thel ow IC 50 (8-27 nm)v alues follow the order SiPc-3-E > SiPc-PEG > SiPc-2-E,w hich is in accordance with their F D and ROS levels. Their high photodynamic anticancer activities are attributed to their low aggregation in the culture mediuma nd specific subcellular localization.…”

“…The dose‐dependent survival curves are shown in Figure . All conjugates essentially had no dark cytotoxicity, and exhibited significantly high photo‐cytotoxicity upon low‐dose light illumination (670 nm, 1.5 J cm −2 , 25 mW cm −2 ) which is usually used in phthalocyanine‐based PDT . The low IC 50 (8–27 n m ) values follow the order SiPc‐3‐E>SiPc‐PEG>SiPc‐2‐E, which is in accordance with their Φ Δ and ROS levels.…”