Remote-Loaded Boron Liposomes: Cell Membrane Interfaces for Enhanced Cellular Association in Boron Neutron Capture Therapy

Efficient delivery of boron is a critical determinant of the therapeutic efficacy of boron neutron capture therapy (BNCT). However, conventional boron-loaded liposomal systems often suffer from low encapsulation efficiency (EE), resulting in a significant loss of costly 10 B-enriched compounds and limited practical applicability. In this study, we established a remote loading strategy for the efficient encapsulation of boron compounds into liposomes. By employing a transmembrane ion gradient, boron-encapsulated liposomes (BLPs) were prepared with an encapsulation efficiency of 42.1% and a boron-to-phospholipid ( B / P ) ratio of 2, demonstrating the feasibility of remote loading for boron delivery. To further enhance liposome–cell interactions, BLPs were modified with cancer cell membrane interfaces derived from MDA-MB-231 cells. The resulting CM-BLPs exhibited significantly enhanced cellular association, achieving a boron accumulation of 125 ng[B]/10 6 cells, and showed stable retention without detectable leakage under physiological conditions. In vitro BNCT irradiation experiments revealed that CM-BLPs exhibited greater therapeutic efficacy than both unmodified BLPs and 4-borono- l -phenylalanine (BPA). These results demonstrate the feasibility of remote loading as a practical and scalable strategy for boron delivery in BNCT with cell membrane interfaces serving as a complementary approach to enhance cellular interactions.