Molecular design of ternary copolymers with high photothermal performance in the near-infrared window for effective treatment of gliomas in vivo.

Photothermal therapy (PTT) is a promising approach for treating glioblastoma multiforme (GBM) with minimal invasiveness and favorable outcomes. Conjugated polymers as photothermal agents offer stability, biocompatibility, and adjustable absorption capacity. However, existing polymers face limitations in achieving high photothermal conversion efficiency and strong absorbance in the near-infrared (NIR) region, posing a risk of damaging healthy tissues surrounding GBM during precise PTT. Herein, a molecular design strategy was developed to create a series of ternary copolymers by incorporating various π-conjugated molecules into both the main chain and side chain. Through this approach, PDTT-253, with rational molar contents of three units and a relatively minor twisted architecture between donors and π-bridges, demonstrated strong NIR absorbance and high PCE of 85.1 % at 808 nm. Furthermore, PDTT-253 nanoparticles exhibited exceptional photothermal stability, photostability, and prolonged storage validity period. In vitro studies revealed high biocompatibility and strong NIR photothermal killing efficacy of PDTT-253 NPs when incubated with U87 cells. Following the injection of PDTT-253 NPs into U87 glioma-bearing mice, a single 808 nm laser irradiation treatment resulted in the inhibition of glioma growth, with the ablated glioma being entirely detached from the surrounding normal tissue after PTT treatment, leading to a comprehensive cure. These results suggest that photostable and biocompatible ternary copolymer nanoparticles based on PDTT-253 show promise for PTT therapy in brain tumors through in situ injection and NIR irradiation. STATEMENT OF SIGNIFICANCE: A molecular design strategy was developed to create a series of ternary copolymers by incorporating various π-conjugated molecules into the conjugated skeleton. Through this approach, PDTT-253, with rational molar contents of three units and a relatively minor twisted architecture between donors and π-bridges, demonstrated enhanced near-infrared (NIR) absorbance and photothermal conversion efficiency of 85.1 % at 808 nm. Furthermore, PDTT-253 nanoparticles exhibited exceptional photothermal stability, high biocompatibility, and strong NIR photothermal killing efficacy against U87 cells. Following the injection of PDTT-253 NPs into U87 glioma-bearing mice, a single 808 nm laser irradiation treatment resulted in the inhibition of glioma growth, with the ablated glioma being entirely detached from the surrounding normal tissue after photothermal therapy treatment, leading to a comprehensive cure.