Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore, 117585.
Small. 2015 Apr;11(13):1603-10. doi: 10.1002/smll.201402092. Epub 2014 Nov 3.
Conjugated polymers (CPs) with strong near-infrared (NIR) absorption and high heat conversion efficiency have emerged as a new generation of photothermal therapy (PTT) agents for cancer therapy. An efficient strategy to design NIR absorbing CPs with good water dispersibility is essential to achieve excellent therapeutic effect. In this work, poly[9,9-bis(4-(2-ethylhexyl)phenyl)fluorene-alt-co-6,7-bis(4-(hexyloxy)phenyl)-4,9-di(thiophen-2-yl)-thiadiazoloquinoxaline] (PFTTQ) is synthesized through the combination of donor-acceptor moieties by Suzuki polymerization. PFTTQ nanoparticles (NPs) are fabricated through a precipitation approach using 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000 ) as the encapsulation matrix. Due to the large NIR absorption coefficient (3.6 L g(-1) cm(-1) ), the temperature of PFTTQ NP suspension (0.5 mg/mL) could be rapidly increased to more than 50 °C upon continuous 808 nm laser irradiation (0.75 W/cm(2) ) for 5 min. The PFTTQ NPs show good biocompatibility to both MDA-MB-231 cells and Hela cells at 400 μg/mL of NPs, while upon laser irradiation, effective cancer cell killing is observed at a NP concentration of 50 μg/mL. Moreover, PFTTQ NPs could efficiently ablate tumor in in vivo study using a Hela tumor mouse model. Considering the large amount of NIR absorbing CPs available, the general encapsulation strategy will enable the development of more efficient PTT agents for cancer or tumor therapy.
具有强近红外(NIR)吸收和高热转换效率的共轭聚合物(CPs)已成为癌症治疗的新一代光热治疗(PTT)试剂。设计具有良好水分散性的 NIR 吸收 CPs 的有效策略对于实现优异的治疗效果至关重要。在这项工作中,通过Suzuki 聚合将供体-受体部分结合在一起合成了聚[9,9-双(4-(2-乙基己基)苯基)芴-alt-共-6,7-双(4-(己氧基)苯基)-4,9-二(噻吩-2-基)-噻二唑并喹喔啉](PFTTQ)。通过沉淀法使用 1,2-二硬脂酰基-sn-甘油-3-磷酸乙醇胺-N-[甲氧基(聚乙二醇)-2000](DSPE-PEG2000)作为封装基质制备 PFTTQ 纳米颗粒(NPs)。由于大的 NIR 吸收系数(3.6 L g(-1) cm(-1)),PFTTQ NP 悬浮液(0.5 mg/mL)在连续 808 nm 激光照射(0.75 W/cm(2))5 分钟后温度可迅速升高至 50°C 以上。PFTTQ NPs 在 NPs 浓度为 400 μg/mL 时对 MDA-MB-231 细胞和 Hela 细胞均表现出良好的生物相容性,而在激光照射下,在 NP 浓度为 50 μg/mL 时观察到有效的癌细胞杀伤作用。此外,PFTTQ NPs 可在使用 Hela 肿瘤小鼠模型的体内研究中有效消融肿瘤。考虑到大量可用的 NIR 吸收 CPs,通用封装策略将能够开发出更有效的 PTT 试剂用于癌症或肿瘤治疗。
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