Boron-Nanoparticle-Loaded Folic-Acid-Functionalized Liposomes to Achieve Optimum Boron Concentration for Boron Neutron Capture Therapy of Cancer.

In this study, we have synthesized and characterized a pure boron nanoparticle containing asolectin phospholipid-based liposome construct prepared using a water-in-oil emulsion method, as a novel alternative agent for BNCT, which contain poly(maleic anhydride-alt-1-octadecene) (PMAO) and polyethylene glycol (PEG) on the surface, and Cy5 near infrared (NIR) fluorescent dye and boron nanoparticles in the core (3PCB). A tumor-specific targeting ligand, folic acid (FA), was conjugated to PEG to produce a folate-functionalized liposome (FA-3PCB) for improved targeted delivery and accumulation of boron in cancer cells. The liposomes showed an average diameter of 100-120 nm and zeta potential of -38.0 +/- 1.5 mV. Cellular uptake monitored by fluorescence microscopy confirmed the targeting capability of FA-conjugated liposomes. Accumulation of FA-conjugated liposomes in C6-brain tumor cells was much higher than that of non-FA conjugated liposomes under the same conditions. ICP-MS (Inductively Coupled Plasma Mass Spectrometry) quantification confirmed that boron accumulated in cancer cells to sufficient intracellular concentration for therapeutic benefit from BNCT. These liposomes show blood-brain barrier (BBB) crossing ability, low cytotoxicity, and excellent stability under physiological conditions. Thus, these liposomes are a promising new boron carrier for BNCT.