pH-Responsive and near-infrared-emissive polymer nanoparticles for simultaneous delivery, release, and fluorescence tracking of doxorubicin in vivo

Ji-Cheng Yu, Yu-Lei Chen, Yu-Qi Zhang, Xi-Kuang Yao, Cheng-Gen Qian, Jun Huang, Sha Zhu, Xi-Qun Jiang, Qun-Dong Shen, Zhen Gu
2014 Chemical Communications  
and doxorubicin was obtained through neutralization with triethylamine. 2,7-Bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9, 9-bis[3'-(dimethylamino) propyl] fluorene was prepared by the method described elsewhere. 1 5,7-Bis(5-bromo-2-thienyl)-2,3-dimethyl-thieno[3,4b]pyrazine was purchased from Beijing Allmers Chemical S&T Co. Ltd. Male ICR mice were supplied by the Experimental Animal Center of Nanjing Medical University (Nanjing, China). Murine hepatic cancer cell line H22 was purchased
more » ... om Shanghai Institute of Cell Biology (Shanghai, China). All animal studies were performed in compliance with guidelines set by the Animal Care Committee at Drum Tower Hospital. Synthesis of Poly{9,9-bis(N,N-dimethylpropan-1-amino)-2,7-fluorene-alt-5,7-bis(thiophen-2-yl)-2,3-dimethylthieno[3,4-b] pyrazine} (BTTPF) 2,7-Bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9,9-bis[3'-(dimethylamino) propyl] fluorene (100 mg), 5,7-bis(5-bromo-2-thienyl)-2,3dimethyl-thieno[3,4-b]pyrazine (82.6 mg), and Pd(PPh 3 ) 4 (55 mg) were dissolved in a degassed mixture of toluene (60 mL) and K 2 CO 3 (2 mol/L, 20 mL). The mixture was stirred at 85~90 o C for 48 h under argon atmosphere. After cooling down to room temperature, the mixture was extracted with chloroform, washed with brine and distilled water, and then recrystallized from acetone to afford a black solid 69 mg (yield 61.6%). 1 H NMR (300 MHz, CDCl 3 , δ): 7.40-7.70 (m, Ar-H), 2.76 (s, pyrazine-CH 3 ), 2.07-2.15 (m, Fluorene-CH 2 , NCH 2 , NCH 3 ), 0.88 (m, CH 2 CH 2 CH 2 ). The molecular weight of BTTPF was determined by GPC (calibrated by polystyrene standard). The weight-average molecular weight of BTTPF was 11600, and the polydispersity was 1.47. Synthesis of m-Dextran. M-dextran was synthesized by aldolization using pyridinium p-toluenesulfonate as a catalyst. Briefly, 1.0 g of dextran (Mn~9-11 kDa) was added to a flame-dried flask and purged with argon. Anhydrous DMSO (10 mL) was added and stirred until complete dissolution of the dextran. Pyridinium p-toluenesulfonate (PPTS, 15.6 mg, 0.062 mmol) was added to the solution followed by 2-ethoxypropene (4.16 mL, 37 mmol). The flask was purged with argon and then sealed with parafilm to prevent evaporation of 2-ethoxypropene. The reaction was stirred at room temperature for 1 h, and then was quenched with triethylamine (1 mL, 7 mmol). The mixture was precipitated and washed three times in basic water (pH ~8) to prevent undesired degradation and collected by centrifugation (6000 rpm, 15min). Residual water was moved by lyophilization, yielding m-dextran (1.43 g) as a white solid.
doi:10.1039/c3cc49870k pmid:24671329 fatcat:cb43jpjtbfglrj2ysdukyi45ua