One approach to improve brain tumor uptake of boron compounds has been to conjugate them to a drug-transport vector by means of receptor-specific transport systems.160,161 Proteins such as insulin, insulin-like growth factor (IGF), TF,162 and leptin can traverse the BBB. BSH encapsulated in TF_PEG liposomes had a prolonged residence time in the circulation and low RES uptake in tumor-bearing mice, resulting in enhanced extravasation of the liposomes into the tumor and concomitant internalization by receptor-mediated endocytosis.163,164 Mice that received BSH containing TF-liposomes following by BNCT had a significant prolongation in survival time compared to those that received PEG-liposomes, bare liposomes and free BSH, thereby establishing proof-of-principle for transcytosis of a boron containing nanovehicle.112
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