Photodynamic therapy (PDT) is based on the delivery of photocytotoxic agents to a target tissue, followed by irradiation. In order to increase the efficiency of PDT in oesophageal cancer therapy, polyethylene glycol (PEG)-grafted, transferrin (Tf)-conjugated liposome formulations of 5,10,15,20-tetra(m-hydroxyphenyl)chlorin (Foscan), a second-generation photosensitiser, were prepared. Expression of transferrin receptors (CD71) in the oesophageal cancer cell line, OE21, was confirmed by immunoblot and confocal laser scanning microscopy. The anti-proliferative effect of Foscan liposomes was evaluated and compared with plain formulations (i.e., without Tf) as well as with free drug. In addition, the intracellular accumulation was studied using high content analysis. Surprisingly, delivering Foscan by transferrin-conjugated PEG-liposomes to oesophageal cancer cells did not improve the photocytotoxicity or the intracellular accumulation of Foscan when compared to unmodified liposomes or indeed free photosensitiser. Tf-targeted drugs and drug delivery systems have shown improvedthe therapy of many cancers. Our study, however, did not corroborate these findings. If this is due to the tumour type, the choice of in vitro model or the delivery systems remains to be confirmed. ; PUBLISHED ; This work was supported by grants from the Health Research Board (translational research award 2007 TRA/2007/11), Science Foundation Ireland (SFI P.I. 09/IN.1/B2650 and SRC (07/SRC/B1154) and Fundação da Ciência e Tecnologia (SFRH/BD/62364/2009). The authors wish to thank to Elena Schwagerus for assistance in the Western blot and Jennifer Conroy for support with confocal laser scanning microscopy