Enhanced photodynamic activity of asymmetric non-ionic Zn(II) phthalocyanine amphiphiles: Effect of molecular design on In vitro activity

We herein introduce the rational design, synthesis, and photophysical characterizations of three asymmetric Zn (II)Pcs (Pc-Glu4, Pc-Mal4, and Pc-PEG4) bearing four neutral hydrophilic substituents, namely glucosyl, maltosyl, and PEG, on the macrocyclic dual rims. The photodynamic activity of the attained structures, as compared to their fully derivatized hydrophilic versions (hexadeca-glucosylated Pc-Glu16 and PEGylated Pc-PEG16 and AzaPc-PEG16), on several cell lines, e.g., HeLa, SK-MEL-28, MCF-7, was investigated. Results revealed that the newly designed macrocycles were characterized by higher photodynamic activity with EC50 values in (sub) micromolar ranges, which is about two orders of magnitude better than for symmetric hydrophilic counterparts. This has been attributed to their higher uptake by cells as well as their significant interaction with bovine serum albumin and biomembranes. A preserved photodynamic activity during the treatment without incubation on endothelial cell lines (HUVEC and EA.hy928) was detected for the asymmetrical gluco-macrocycles, indicating a good potential for vascular-targeted PDT.