Xing Q Pan1, Huaqing Wang, Robert J Lee. 1. Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus 43210, USA.
Abstract
BACKGROUND: Folate receptor (FR) is amplified in a variety of human tumors. Folate-derived liposomes have been shown to selectively deliver entrapped agents into tumor cells via receptor-mediated endocytosis. In this preliminary study, the biodistribution of FR-targeted liposomes were evaluated as a potential delivery agent for Na3 (B20H17NH3) for boron neutron capture therapy (BNCT) of FR(+) tumors. MATERIALS AND METHODS: Na3 (B20H17NH3) was incorporated into liposomes by passive entrapment, following which they were administered intravenously into BALB/c mice bearing subcutaneous implants of FR(+) M109 murine lung carcinoma. Tumor and normal tissue boron content was measured by direct current plasma atomic emission spectroscopy. RESULTS: Mice that received FR-targeted and non-targeted control liposomes showed indistinguishable levels of tumor boron uptake (up to 85 microg/g tumor), which reached a maximum at the 24 hour time-point, while the tumor-to-blood (T/B) ratio continued to rise until the 72 hour time-point. CONCLUSION: High-level boron delivery is possible using liposomes as a delivery agent. FR targeting does not significantly enhance overall tumor localization but may improve boron delivery at the cellular and subcellular levels, which warrant further investigation.
BACKGROUND:Folate receptor (FR) is amplified in a variety of humantumors. Folate-derived liposomes have been shown to selectively deliver entrapped agents into tumor cells via receptor-mediated endocytosis. In this preliminary study, the biodistribution of FR-targeted liposomes were evaluated as a potential delivery agent for Na3 (B20H17NH3) for boron neutron capture therapy (BNCT) of FR(+) tumors. MATERIALS AND METHODS:Na3 (B20H17NH3) was incorporated into liposomes by passive entrapment, following which they were administered intravenously into BALB/c mice bearing subcutaneous implants of FR(+) M109 murinelung carcinoma. Tumor and normal tissue boron content was measured by direct current plasma atomic emission spectroscopy. RESULTS:Mice that received FR-targeted and non-targeted control liposomes showed indistinguishable levels of tumorboron uptake (up to 85 microg/g tumor), which reached a maximum at the 24 hour time-point, while the tumor-to-blood (T/B) ratio continued to rise until the 72 hour time-point. CONCLUSION: High-level boron delivery is possible using liposomes as a delivery agent. FR targeting does not significantly enhance overall tumor localization but may improve boron delivery at the cellular and subcellular levels, which warrant further investigation.