Boron neutron capture therapy (BNCT) is a promising binary radiotherapy that uses the isotope 10 B and thermal neutron irradiation to induce lethal nuclear reactions in tumor cells. However, the effectiveness of BNCT often relies on the precise match between 10 B and thermal neutrons. In this study, we developed a boron delivery system, integrating boron nitride ( 10 BN) nanoparticles with microneedle (MN) patches (referred to as BN-MN). At equivalent dosages, BN-MN was able to maintain an intratumoral boron concentration above 20 ppm for over two hours, effectively aligning with the neutron irradiation time window. BN-MN also demonstrated efficient penetration and uniform distribution throughout the entire tumor tissue, with a tumor-to-normal tissue ratio (T/N) of 42 and a tumor-to-blood ratio (T/B) of 150, significantly superior to clinical boron drugs. More importantly, BN-MN efficiently delivered boron into tumor tissues at a precise cellular resolution, achieving an intracellular boron concentration 6.8 times higher than that obtained by BPA-loaded microneedles (BPA-MN). In vivo experiments demonstrated that the BN-MN system effectively inhibited tumor growth under neutron irradiation, with minimal systemic side effects. In summary, BN-MN perfectly matched neutron irradiation in terms of sufficient concentration, optimal retention time, and uniform spatial distribution, thereby enhancing the therapeutic efficacy and safety of BNCT.
The combination of radiotherapy and immune checkpoint blockade (ICB) therapy has demonstrated considerable efficacy in oncological treatment. However, the clinical PD-L1 antibody (anti-PD-L1) for glioblastoma (GBM) imprecisely accumulated in intracranial radiotherapy target and is often compromised by the formidable blood-brain barrier (BBB). To address these challenges, the study innovatively engineers a hierarchical precision delivery nanoplatform (FB-aPD-L1). This nanoplatform leverages sulfated fucoidan, which exhibited targeted affinity for P-selectin, an adhesion molecule expressed with spatiotemporally restricted specificity in response to radiotherapy. Following precise capture FB-aPD-L1 and crossing BBB, there is ultrasensitive release of BPA 4 -aPD-L1 and fucoidan in the tumor microenvironment. The targeted conjugation of 5-borono-2-pyridinecarboxylic acid (BPA) and sialic acid (SA) augmented tumor-specific targeting and retention of anti-PD-L1, while fucoidan reprogrammed the immune microenvironment, thereby synergizing with the anti-PD-L1 to increase CD8 + T cell infiltration and enhance radio-immunotherapy efficacy. This work exemplifies a novel paradigm for brain-targeted precise drug delivery.
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