Microneedle-adapted PAMAM-BSH delivery facilitates spatiotemporal matching for melanoma boron neutron capture therapy

Boron Neutron Capture Therapy (BNCT) is a binary radiotherapy based on the combination of ¹⁰B drugs and thermal neutrons. Coordinating ¹⁰B with neutron irradiation will optimize the efficacy of BNCT, but further improvements are still required. Here, we develop a delivery system incorporating microneedles (MNs) and a modified boron agent PAMAM-BSH, enabling precise spatiotemporal matching of ¹⁰B with neutron irradiation for melanoma BNCT. The PAMAM-BSH is a cationic polymer ¹⁰B agent with amphiphilicity, forming nanomicelles in an aqueous solution. It exhibits high boron content and demonstrates good uptake and retention capabilities in cancer cells. When administering PAMAM-BSH-loaded MNs to melanoma-bearing mice, the duration for which the ¹⁰B content in tumors exceeds 20 ppm can extend up to 2 h. Notably, the system facilitates the precise administration of ¹⁰B into tumor cells, achieving concentrations exceeding 35 ng 10^-6 cells. These contribute to an excellent alignment of spatiotemporal matching of ¹⁰B with neutron irradiation in BNCT. Meanwhile, the T/N (tumor-to-normal tissue) and T/B (tumor-to-blood) ratios can reach 30 and 100, respectively, which are much higher than the clinical BPA (T/N is 1.1-2.9, T/B is 1.1-3.6). Utilizing the system ultimately demonstrated a significant enhancement in melanoma BNCT, along with improved safety.