Boron neutron capture therapy (BNCT) is an atomic targeted radiotherapy that shows fantastic suppression impact on locally intrusive threatening tumors. One key factor for effective BNCT is to aggregate an adequate concentration (>20 ppm) of 10B in the cytoplasm of the tumor. Carborane-loaded polymer nanoparticles are promising because of their outstanding biocompatibility and plasma steadiness. In this study, a new class of carborane-loaded nanoscale covalent organic polymers (BCOPs) was prepared by a Schiff base condensation reaction, and their solubility was greatly improved in common solvents via alkyl chain engineering and size tailoring. The obtained BCOP-5T was further functionalized by biocompatible 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene-glycol)-2000] (DSPE-PEG, molecular weight 2000) to form stable aqueous-phase nanoparticles with a hydrodynamic diameter of around 100 nm. After chelating with radioactive copper-64, DSPE-BCOP-5T was tracked by positron emission tomography (PET) imaging and showed significant accumulation in the tumor. DSPE-BCOP-5T + neutron radiation showed remarkable tumor suppression in 4T1 tumor-bearing mice (murine breast cancer). No obvious physical tissue damage and abnormal behavior were observed, demonstrating that the boron delivery was successful and tumor-selective. To conclude, this study presents a theranostic COP-based platform with a well-defined composition, good biocompatibility, and satisfactory tumor accumulation, which is promising for PET imaging, drug delivery, and BNCT.
Keywords: boron neutron capture therapy (BNCT); copper-64; covalent organic polymers (COPs); positron emission tomography (PET); theranostics.