Biocompatible Conjugated Polymer Nanoparticles for Efficient Photothermal Tumor Therapy

Biocompatible Conjugated Polymer Nanoparticles for Efficient Photothermal Tumor Therapy
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DOI:
10.1002/smll.201402092
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发表时间:
2015-04-01
期刊:
影响因子:
13.3
通讯作者:
Liu, Bin
Liu, Bin
中科院分区:
材料科学1区
文献类型:
--
作者:
Geng, Junlong;Sun, Chunyang;Liu, Bin

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共轭聚合物(CP)具有强近红外(NIR)吸收和高的热转换效率,已成为用于癌症治疗的新一代光热治疗(PTT)剂。设计一种有效的策略来设计具有良好水溶性的近红外吸收CP是实现优异治疗效果的必要条件。本文通过Suzuki聚合法合成了聚[9,9-双(4-(2-乙基己基)苯基)芴-alt-co-6,7-双(4-(己氧基)苯基)-4,9-二(噻吩-2-基)噻二唑并喹喔啉](PFTTQ)。使用1,2-二硬脂酰-sn-甘油基-3-磷酸乙醇胺-N-[甲氧基(聚乙二醇)-2000](DSPE-PEG(2000))作为包封基质,通过沉淀方法制备PFTTQ纳米颗粒(NP)。由于大的近红外吸收系数(3.6 L g(-1)cm(-1)),PFTTQ NP混悬液的温度(0.5mg/mL)在连续808 nm激光照射下可迅速升高至50 ℃以上PFTTQ NP在400 μ g/mL NP下对MDA-MB-231细胞和Hela细胞均显示出良好的生物相容性,而在激光照射下,在NP浓度为50 μ g/mL时观察到有效的癌细胞杀伤。此外,在使用HeLa肿瘤小鼠模型的体内研究中,PFTTQ NP可以有效地消融肿瘤。考虑到大量可用的吸收NIR的CP,一般的包封策略将使得能够开发用于癌症或肿瘤治疗的更有效的PTT剂。
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(polyethyleneglycol)-2000] (DSPE-PEG(2000)) 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 degrees 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 mu g/mL of NPs, while upon laser irradiation, effective cancer cell killing is observed at a NP concentration of 50 mu g/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.