Boron delivery to a murine lung carcinoma using folate receptor-targeted liposomes.
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.


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.


CONCLUSIONS
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.
Pan
Xing Q
XQ
Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus 43210, USA.
Wang
Huaqing
H
Lee
Robert J
RJ
D000818:Animals; D001895:Boron / Q000008:administration & dosage / Q000493:pharmacokinetics; D001896:Boron Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D002352:Carrier Proteins / Q000378:metabolism*; D005260:Female; D058973:Folate Receptors, GPI-Anchored; D008081:Liposomes / Q000008:administration & dosage / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism* / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D011956:Receptors, Cell Surface; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D001896:Boron Compounds; D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D008081:Liposomes; D011956:Receptors, Cell Surface; D001895:Boron