小分子基温敏聚合物纳米粒子的制备及在近红外二区荧光成像与光热治疗中的应用

以有机小分子4,9-二(5-9H-芴-2-基-噻吩-2-基)-6',7-联苯1,2,5]噻二唑并3,4-g]喹喔啉(TQF)为前驱体, 通过化学方法将其修饰为可引发可逆加成-断裂链转移聚合(RAFT)反应的小分子链转移剂TQF-苯基硫代链 转移剂（CTA）. 以TQF-CTA为链转移剂, 以偶氮二异丁腈为引发剂, 引发N-异丙基丙烯酰胺(NIPAAm)和 甲基丙烯酸寡聚乙二醇酯(OEGMA)发生RAFT聚合反应, 合成了具有良好水溶性和较低临界溶解温度(LCST)的小分子基共聚物TQF-P(NIPAAm-co-OEGMA), TPNO]. 将其直接溶于水中可制备成温敏的球形纳米粒子 TPNO NPs. 研究结果表明, TPNO NPs在温度大于LCST(35 ℃)时表现出一个明显的粒径变化和显著的荧光 增强行为(2.2倍), 并成功实现了对活体小鼠血管与肿瘤的明亮近红外二区(NIR-Ⅱ)荧光成像(FI). 同时, TPNO NPs有着良好的光热转换效率(PCE=29.8%), 通过体外细胞实验证明了其对细胞具有较好的光热治疗(PTT)效果.

Small-molecule-based Thermosensitive Polymer Nanoparticles for NIR-Ⅱ Fluorescence Imaging and Photothermal Therapy

An organic small molecule 4，9-bis［5-（9H-fluoren-2-yl）thiophen-2-yl］-6'，7-diphenyl-［1，2，5］thiadiazolo［3，4-g］quinoxaline（TQF） was selected as a precursor， followed by chemical modification into a small molecular chain transfer agent—TQF-phenylthio chain transfer agent（CTA）， which enabled the reversible addition-fragmentation chain transfer polymerization（RAFT）. Then， the copolymer［TQF-P（NIPAAm-co-OEGMA）， abbreviated as TPNO］ with good water solubility and lower critical solution temperature（LCST） was synthesized by RAFT with TQF-CTA as the chain transfer agent， azobisisobutyronitrile as initiator， as well as thermosensitive N-isopropylacrylamide（NIPAAm） and hydrophilic oligoethylene glycol methacrylate（OEGMA） as the monomers. TPNO was directly dissolved in water to prepare the thermosensitive spherical nanoparticles TQNO NPs. The results showed that TQNO NPs exhibited an obvious particle size change and a significant fluorescence enhancement behavior（2.2 times） when the test temperature was greater than LCST（35 ℃）， and successfully achieved bright second near-infrared（NIR-Ⅱ） fluorescence imaging（FI） of blood vessels and tumors in living mice. Meanwhile， TQNO NPs displayed a good photothermal conversion efficiency（PCE=29.8%）， and the in vitro cell experiments had successfully proved its desirable photothermal therapy（PTT） effect.