Process Optimization of Novel Boronophenylalanine Liposomes Through Box-Behnken Response Surface Design and...

Boron neutron capture therapy (BNCT) is a binary targeted radiotherapy that uses boron agents to treat refractory malignancies. This study developed a novel boronophenylalanine (BPA)-loaded liposome doped with o-carborane (CB) for BNCT. We applied response surface methodology (RSM) to identify factors affecting BPA loading and optimized encapsulation efficiency (EE) to minimize BPA loss. In in vitro experiments, these liposomes demonstrated promising characteristics for BNCT. The nanoparticle properties of CB-BPA-Lips remain stable for at least 48 h, and CB-BPA-Lips can effectively reduce the release of the agents loaded within them. Both cell viability assays and apoptosis assays have shown that CB-BPA-Lips have good biocompatibility and a lower inhibitory effect on cell viability than BPA. Cellular boron uptake peaked at 47.3642 ng B/10⁶ cells in A549 lung cancer cells and peaked at 38.8875 ng B/10⁶ cells in Bronchial Epithelium transformed with Ad12-SV40 2B (BEAS-2B) human normal bronchial epithelial cells at 24 h post-treatment, with both exceeding uptake in the BPA control group. Overall, this work presents an optimized liposomal formulation that enhances boron delivery to cancer cells and provides a potential candidate boron agent for BNCT pending in-depth in vivo studies.