Enhanced phototoxicity and specificity of AlPCS4 when loaded in liposomes conjugated with a MET-targeting nanobody

Photodynamic therapy (PDT) improves the survival of cholangiocarcinoma patients. Here, to improve the pharmacokinetics and efficacy of PDT, AlPCS4 was encapsulated into liposomes conjugated with a nanobody. AlPCS4 was loaded in liposomes conjugated with a nanobody targeting hepatocyte growth factor receptor (MET). The uptake of the MET-targeted liposomes (MET-TLs) and non-targeted liposomes (NTLs) was studied with confocal microscopy and flow-cytometry. Phototoxicity of MET-TLs and NTLs was tested by exposing MET-positive (TOV+MET, EGI1) and MET-negative (TOV112D) cells to a range of AlPCS4 concentrations. After incubation, cells were illuminated and cell viability was measured with MTS assay. MET-TLs were more internalized by MET-positive cells and induced higher phototoxicity than NTLs (LC50 was 10 × lower for MET-TLs). No phototoxicity was observed on MET-negative cells and in non-illuminated controls for the concentrations tested. This study demonstrated that MET-TLs can increase the specificity of AlPCS4 towards cancer cells and enhance phototoxicity.