Department of Biomedical Engineering, School of Life Science and Technology, China Pharmaceutical University, Tongjia Lane No. 24, Nanjing, 210009, People's Republic of China.
Pharm Res. 2010 Jan;27(1):46-55. doi: 10.1007/s11095-009-0005-1. Epub 2009 Nov 11.
To synthesize P[(Folate-Allylamine)-co-(N-isopropylacrylamine)- co-Acrylamide] (P(FoAAn-co-NIPA-AAm), folate-NHG) with appropriate diameter and lower critical solution temperature (LCST) for targeting to folate receptor (FR) expressing tumors.
Folate-NHG was synthesized by free-radical precipitation polymerization method reported in our previous work and other reports. LCST, diameter and morphology of folate-NHG were characterized by UV-vis spectrophotometer, laser particle size analyzer (LPSA) and transmission electron microscope (TEM), respectively. No.12 near infrared dye (NIRD-12) was entrapped into folate-NHG by hydrophobic association to trace the in vivo dynamic behavior of folate-NHG. This process was evaluated by a homemade near infrared (NIR) imaging system.
Spherical folate-NHG with diameter of about 50 nm and LCST of about 40 degrees C was successfully synthesized. The photo stability of NIRD-12 was strengthened after being entrapped into folate-NHG, which enabled NIRD-12 to better trace the in vivo dynamic process of folate-NHG. Folate-NHG showed good targeting capability for all three folate receptor expressing tumor models (SMMC-7721, Bel-7402 and HeLa) with different sizes, and this accumulation could last for more than 96 h. D-folate-NHG, synthesized with double amount of FoAAn, showed better targeting effect for SMMC-7721 tumor model than that of folate-NHG.
Folate-NHG could actively accumulate in three models of folate receptor positive tumors with different sizes and keep retention for more than 96 h, which enables it to be used as a diagnostic reagent or anti-tumor drug carrier for tumor therapy.
合成具有适当直径和较低临界溶液温度 (LCST) 的 P[(叶酸-丙烯酰胺)-共-(N-异丙基丙烯酰胺)-共-丙烯酰胺]（P(FoAAn-co-NIPA-AAm)，叶酸-NHG），以靶向表达叶酸受体 (FR) 的肿瘤。
叶酸-NHG 是通过我们之前的工作和其他报告中报道的自由基沉淀聚合方法合成的。LCST、直径和形态学通过紫外可见分光光度计、激光粒度分析仪（LPSA）和透射电子显微镜（TEM）分别进行了表征。通过疏水缔合将 No.12 近红外染料 (NIRD-12) 包封到叶酸-NHG 中，以追踪叶酸-NHG 的体内动态行为。这个过程是通过自制的近红外（NIR）成像系统进行评估的。
成功合成了直径约为 50nm、LCST 约为 40°C 的球形叶酸-NHG。NIRD-12 被包封到叶酸-NHG 中后，其光稳定性得到增强，使其能够更好地追踪叶酸-NHG 的体内动态过程。叶酸-NHG 对三种大小不同的叶酸受体表达肿瘤模型（SMMC-7721、Bel-7402 和 HeLa）均表现出良好的靶向能力，这种积累可持续超过 96 小时。用两倍量的 FoAAn 合成的 D-叶酸-NHG 对 SMMC-7721 肿瘤模型的靶向效果优于叶酸-NHG。
叶酸-NHG 可以主动积聚在三种大小不同的叶酸受体阳性肿瘤模型中，并保持超过 96 小时的保留，使其可以用作肿瘤治疗的诊断试剂或抗肿瘤药物载体。
