Glycoconjugated Phthalocyanines as Photosensitizers for PDT – Overcoming Aggregation in Solution

Abstract

A series of new glycoconjugated zinc(II) phthalocyanines (Pcs) was synthesized and fully characterized. The major focus of the structural design for these new Pcs was upon the reduction of aggregate formation in solution. Therefore, the aglycons of the Pc‐linked sugars, the number and the position of the carbohydrate substituents on the Pc and the linker between sugar and Pc were varied. Specifically, di‐ and octasubstituted zinc(II) phthalocyanines with triazole and C–C linkages were synthesized and their aggregation behaviour was investigated by UV/Vis‐, CD‐ and NMR spectroscopy. The C‐glycosidically decorated Pcs described here are the first compound types of this kind. These C‐glycosidically substituted Pcs were shown to not form any aggregation in solution and hence, are considered to be potential photosensitizers in photodynamic therapy. All Pcs synthesized in this study exhibited excellent photophysical properties for use as photosensitizers (λmax > 675 nm with εmax > 105 m–1 cm–1). Preliminary cytotoxicity studies of the Pcs presented here showed that all Pcs are photodynamically effective.

Potential of Photodynamic Therapy Based on Sugar-Conjugated Photosensitizers

“…The C-glycosidically substituted Pcs did not form any aggregation in solution. Therefore, they were considered as potential PSs in PDT [ 78 ]. As a result, it is expected that the conjugation of sugar and Pc will lead to the development of innovative drugs for PDT and PDD.…”

Phosphate-Assisted Transformation of Methylene Blue to Red-Emissive Carbon Dots with Enhanced Singlet Oxygen Generation for Photodynamic Therapy

“…3 Hematoporphyrin derivatives have pioneered the PDT studies, but their hydrophobic nature restricts the efficiency of treatment. 4 Other photosensitizers like porphyrin, 5 porphin, 6 chlorin e6, methylene blue (MB), 7 and metal phthalocyanine 8 were also proposed for the PDT applications. All these photosensitizers have shown improvement in different aspects of PDT performances, but some side effects are also reported.…”

Optical properties of photodynamic therapy drugs in different environments: the paradigmatic case of temoporfin

“…54 The latter triplet state may produce cytotoxic species by either a type I or type II reaction typical of photosensitizer agents used in photodynamic therapy. 55 As mentioned, the most serious drawback of mTHPC, and many other organic sensitizers, is their hydrophobic nature, which severely limits their transportation in the bloodstream and causes aggregation-induced quenching (ACQ) in biological environments, 56 hence resulting in weak emissions and inadequate generation of reactive oxygen species (ROS). 57 To overcome the mTHPC aggregation issue, specific drug delivery strategies are currently being pursued, 58 in particular, the use of molecular hosts based on beta-cyclodextrin (b-CD) has been proposed.…”