Bis-diketopyrrolopyrrole conjugated polymer nanoparticles as photothermic nanoagonist for specific and synergistic glioblastoma therapy

Abstract Development of high-performance photoactive agents with tumor-specific capability for effective nanotherapeutics has received much attention in the past decades. Herein, we report a nanotherapeutic based on bis-diketopyrrolopyrrole (BDPP) conjugated polymer nanoparticles (PBDPP NPs) with remarkable near-infrared (NIR) absorption at 808 nm and high photothermal energy conversion efficiency up to 60%. In particular, precise glioblastoma-specific capability and killing ability for glioblastoma cells were effectively achieved in vitro by treating with only PBDPP NPs to induce cell apoptosis or by interaction with PBDPP NPs under NIR laser irradiation to trigger cell necrosis. Impressively, a half-maximal inhibitory concentration as low as of ∼0.15 μg mL−1 was achieved, and the magnitude is 5 to 4.4 × 104-fold lower than those of reported agents. In vivo experiment with mice further shows that the PBDPP NPs show good efficacy of photothermal therapy and complete tumor elimination using a record-low dosage of 0.35 mg mL−1 under 808 nm irradiation of low power (0.5 W cm−2). This study thus demonstrates a promising strategy of low-dose, high-efficacy polymer-based nanoagonist for specific phototherapy of glioblastoma.