Comparative cellular uptake studies of a carborane cholesteryl ester by human glioma cell lines
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Low-density lipoprotein (LDL) is the major cholesterol carrier in human plasma. To utilize the elevated expression of LDL receptor on many types of cancer cells, reconstituted LDL has been used as a potential carrier system to deliver anti-cancer drugs selectively to tumor cells. A new cholesterol-carborane conjugate (BCH) mimicking the native cholesteryl ester has been developed for boron neutron capture therapy (BNCT) in our laboratory. The compound is extremely hydrophobic and can be formulated into liposomes. Liposomes carry it to interact with LDL, resulting in the transfer of the drug into the LDL, and thereby, the uptake of BCH by cells via receptor-mediated endocytosis of the LDL. In this study, the cellular uptake of boron was evaluated in human glioma cell line SF-767 based on a series of comparative cell culture studies with BCH and p-carborane, either in DMSO or in conventional liposomes. The cellular uptake of boron from PEG-liposomal formulation was also evaluated. The dependence of uptake on incubation time and the cytotoxicity of the delivery systems were also investigated in the above experiments. The results indicated that the cellular uptake of boron by human glioma cell SF-767 was significantly higher (2.5-8.3 folds) from BCH than that from p-carborane when they were dissolved in DMSO. The encapsulation efficiency of BCH was 10 folds of that of p-carborane when they were formulated in liposomes. In cell culture studies with SF-767 and SF-763, there was no significant difference between the results of experiments (uptake of boron and cytotoxicity) using BCH-loaded conventional liposomal formulation and PEG liposomal formulation.