Novel boron-modified aza-BODIPY photosensitizers for low-dose light-dependent anti-cancer photodynamic therapy

The aggregation-induced decrease in photosensitization activity is one of the major challenges limiting the clinical application of photosensitizers (PSs). Thus, developing highly efficient PSs for anti-cancer photodynamic therapy (PDT) remains an urgent need. To address this challenge, we designed and synthesized a novel family of efficient aza-BODIPY PSs by inhibiting aggregation with a boron-modified strategy. These novel aza-BODIPY PSs demonstrated significantly enhanced in vitro photodynamic efficacy. Of particular note was derivative A1, which emerged as a highly promising NIR PS with high singlet oxygen yield (rel.rate = 1.79) that obviously superior to the reported compound BDP 4 (rel.rate = 1.23) in PBS. Additionally, A1 showed exceptional cytotoxicity against various cells (IC₅₀ > 4.5 nM) at a low light dose of 21.6 J/cm². In vivo anti-tumor experiments showed that significant tumor growth suppression following intravenous administration of A1 (2 mg/kg) and subsequent irradiation (21.6 J/cm², λ = 660 nm), outperforming well-known PSs such as ADPM06 and Ce6. Both in vitro and in vivo studies revealed that A1 exhibited an excellent PDT effect at remarkable low drug and light doses.