Photo-responsive tetraether lipids based vesicles for prophyrin mediated vascular targeting and direct phototherapy

Pictorial design of tetraether lipids (TELs) based liposomes for prophyrin mediated vascular targeting. [Display omitted] •Sulfolobus acidocaldarius tetraether lipids (TELs) based liposomes were developed and characterized.•Protoporphyrin IX based TELs liposomes established photoresponsive platform for photodynamic applications.•High mole fraction of TELs improved Vascular Targeting Photodynamic therapy (VTP) of PpIX.•TELs preserved PDT outcomes versus PpIX dose and the scheduled radiant energy applied at significant levels in cell lines. Tetraether lipids (TELs) derived from the thermoacidophilic archaeon Sulfolobus acidocaldarius are dominated by polyisoprenoid skeleton. The unique molecular stability of TELs is attributed to the presence of cyclopentane rings, methyl side groups and sugar residues that create extensive hydrogen bond network. In addition, the presence of ether linkages and the lacking of double bonds make them an epitome candidate for photodynamic therapy (PDT). A subtle blend of formulation design to trigger efficient photo responses of protoporphyrin IX (PpIX) exploiting TELs was developed. The platform has demonstrated in principle a practical potential in PDT in terms of prompt Vascular Targeting Photodynamic therapy (VTP) in-ovo chick chorioallantoic membrane (CAM) model. Short PpIX-light interval was associated with thrombosis and massive vascular occlusion in and out the irradiated area after TEL9mol% liposomes have been intravenously injected. Profoundly, TEL62mol% liposomes have proved to be the most effective liposomes that demonstrated localized suppression of angiogenesis in the irradiated area without quiescent vasculature damage. The massive thrombotic effect was no longer observed and eventually the chick has survived. After long PpIX-light interval, TEL62mol% has deliberately gained metronomic PDT at low rate of PpIX dosimetry and the radiant exposure doses in human ovarian carcinoma (SKOV-3) cells as determined by PpIXIC50. These findings could be explained by the fact that TELs impart a remarkable stability to the liposomal bilayer that makes them a potential platform for photodynamic applications.