Bifidobacterium-mediated high-intensity focused ultrasound for solid tumor therapy: comparison of two nanoparticle delivery methods

Abstract

Purpose This study was conducted to prepare a novel tumor-biotargeting high-intensity focused ultrasound (HIFU) synergist for indirectly delivering lipid nanoparticles based on the targeting ability of Bifidobacterium longum to the hypoxic region of solid tumors. The effects of two different delivery methods on the imaging and treatment of solid tumors enhanced by lipid nanoparticles were compared. Methods Biotinylated lipid nanoparticles coated with PFH were prepared, cross-linked with B. longum in vitro using a streptavidin-conjugated B. longum antibody (SBA), and observed and detected by laser confocal microscopy and flow cytometry. Solid tumors were treated with HIFU and PFH/BL-NPs. The effects of different delivery methods on the tumor targeting and efficiency of retention of PFH/BL-NPs were observed using Small animal live imaging and frozen sections from small animals. Results The PFH/BL-NPs prepared in this study showed good biocompatibility and safety. PFH/BL-NPs and B. longum were cross-linked in a cluster-like manner (confocal laser scanning microscope) in vitro, with a cross-linking rate of 84 ± 6.23% (flow cytometry). The delivery of B. longum followed by that of PFH/BL-NPs not only enhanced the ability of PFH/BL-NPs to target solid tumors (small animal live imaging), but also increased the retention time of PFH/BL-NPs in the tumor (frozen slices), enhancing the effect of the HIFU synergist. Conclusion Delivery of B. longum followed by that of PFH/BL-NPs can enhance the imaging of solid tumors and effectively improve the efficiency of HIFU treatment of solid tumors, providing a basis for further clinical work.