The impact of glucose conjugation on the activity and uptake of zinc phthalocyanine in HaCaT keratinocytes stimulated with proinflammatory cytokines

Glucose metabolism has been proven as an essential process for proliferating keratinocytes, which highlights the importance of glucose transporter-1 (GLUT1) not only in the onset of psoriasis but also in the progression and severity of this inflammation-driven disease. Recent evidence showed that overexpressed GLUT1 transporter may be a potential target for the treatment of psoriasis and other hyperproliferative skin diseases. For this reason, we attempted to synthesize and evaluate the photocytotoxic activity and intracellular uptake of glucose-conjugated zinc phthalocyanine (Glu-ZnPc), in order to prove its preferential accumulation in highly proliferative psoriatic keratinocytes. HaCaT cells stimulated with exogenous cytokines (TNF-α, IL-6, IL-17, IL-23, IL-36) were used as in vitro model. We managed to synthesize Glu-ZnPc that is stable, water soluble, cytotoxic, and has a more efficient transport system than unconjugated ZnPc. We believe that GLUT1 overexpression could potentially be utilized by using selective glucose- conjugated photosensitizers against psoriasis.