Pyropheophorbide a (Pyro) is a near-infrared (NIR)
fluorescent dye and
photosensitizer with high quantum yield that makes the
dye suitable for
tumor treatment both as an imaging and
therapy agent. We have designed and synthesized a series of a Pyro-based NIR probes, based on the conjugation of Pyro with
lipids. The nature of our probes requires the use of a lipophilic carrier to deliver the probes to
cancer cell membranes. To address this, we have utilized
lipid-based nanoparticles (LNPs) consisting of PEGylated
lipids, which form the nanoparticle shell, and a
lipid core. To endow the LNPs with targeting properties,
nitrilotriacetic acid (NTA)
lipids were included in the composition that enables the non-covalent attachment of His-tag targeting
proteins preserving their functional activity. We found that the nature of the core molecules influence the nanoparticle size, shelf-life and stability at physiological temperature. Two different Pyro-
lipid conjugates were loaded either into the core or shell of the LNPs. The conjugates revealed differential ability to be accumulated in the cell membrane of the target cells with time. Thus, the modular organization of the core-shell LNPs allows facile adjustment of their composition with goal to fine tuning the nanoparticle properties for in vivo application.