We developed an integrin αvβ3-specific liposomes, TR-conjugated liposomes (TR-LPs), loading IR783 for NIR imaging-guided both PTT and PDT. The TR-LPs was composed of soyabeanphosphatidylcholine, cholesterol, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine- N- [methoxy(polyethylene glycol)-2000] (DSPE-PEG) and TR-functionalized DSPE-PEG. IR783, NIR PTT/PDT diagnostic agents, were encapsulated in the hydrophilic core of the TR-LPs. DSPE-PEG had ability of reducing the absorption of TR-LPs by the reticuloendothelial system and increase the cycle time in body. RGD fragment on the TR peptide (TR = c(RGD)-AGYLLGHINLHHLAHL(Aib)HHIL-cys) enhanced the tumor selectivity of liposomes by specifically targeting integrin αvβ3-overexpressing cancer cells. Simultaneously, the rest of fragment on the TR peptide can be changed to the positive charge in the tumor microenvironment (pH 6.5), improving cellular uptake of photoagents at tumor site. We executed a set of in vitro and in vivo experiments to verify if, by functionalizing liposomes with an integrin αvβ3-specific and pH responding peptide, it is possible to achieve NIR imaging guided PTT/PDT for tumor treatment. TR-conjugated liposomes exhibited favorable physical and chemical stability, loading capacity, biocompatibility and tumor targeting. TR-LPs can safely and efficiently delivery IR783 to tumor sites to achieve their therapeutic function. IR783-TR-LPs is promising as a potentially safe and effective phototherapeutic agents for NIR fluorescence-guided tumor therapy applications.
