Tumor Eradication by Boron Neutron Capture Therapy with ¹⁰B-enriched Hexagonal Boron Nitride Nanoparticles Grafted with Poly(Glycerol)

Boron neutron capture therapy (BNCT) has emerged as a treatment modality with high precision and efficacy of intractable tumors. At the core of effective tumor BNCT are B-10 carriers with facile preparation as well as advantageous pharmacokinetic and therapeutic profiles. Herein, the design and preparation of sub-10 nm B-10-enriched hexagonal boron nitride nanoparticles grafted with poly(glycerol) (h-(BN)-B-10-PG), and their application to cancer treatment by BNCT are reported. By virtue of their small particle size and outstanding stealth property, h-(BN)-B-10-PG nanoparticles accumulate efficiently in murine CT26 colon tumors with a high intratumor B-10 concentration of 8.8%ID g(-1) or 102.1 & mu;g g(-1) at 12 h post-injection. Moreover, h-(BN)-B-10-PG nanoparticles penetrate into the inside of the tumor parenchyma and then are taken up by the tumor cells. BNCT comprising a single bolus injection of h-(BN)-B-10-PG nanoparticles and subsequent one-time neutron irradiation results in significant shrinkage of subcutaneous CT26 tumors. h-(BN)-B-10-PG-mediated BNCT not only causes direct DNA damage to the tumor cells, but also triggers pronounced inflammatory immune response in the tumor tissues, which contributes to long-lasting tumor suppression after the neutron irradiation. Thus, the h-(BN)-B-10-PG nanoparticles are promising BNCT agents to eradicate tumor through highly efficient B-10 accumulation.