目的 利用4种高分子可降解生物材料,制备适于MR分子成像的荷钆纳米载体,探讨不同的含钆纳米粒的优缺点.方法 采用生物相容性的高分子材料:固体脂质纳米粒(SLN)、聚乳酸-聚乙二醇(PLA-PEG)、聚乳酸-聚乙二醇-聚赖氨酸(PLA-PEG-PLL),分别利用溶剂乳化挥发法、改良溶剂扩散法、分子自组装法及化学合成等方法链接钆基制备4种载体纳米粒,即吸附型SLN荷钆纳米粒、吸附型PLA-PEG荷钆纳米粒、接枝型PLA-PEG荷钆纳米粒及接枝型PLA-PEG-PLL荷钆纳米粒.利用电镜等技术检查其理化性质,然后进行MR成像探讨不同纳米粒的成像效率.结果 电镜检测结果显示吸附型SLN荷钆纳米粒、吸附型PLA-PEG荷钆纳米粒、接枝型PLA-PEG荷钆纳米粒及接枝型PLA-PEG-PLL荷钆纳米粒的平均粒径分别为(196.1±2.01) nm、(187.9 ± 2.30) nm、(265.9 ± 6.7) nm、(69.8±5.3) nm,zeta电位分别为(17.12±0.61) mV、(-12.36 ± 3.58) mV、(-18.71 ± 2.3) mV、(23.03±4.6) mV.各纳米粒均具有良好的分散性和血浆稳定性.吸附型SLN及PLA-PEG荷钆纳米粒制备工艺简单、MR显影效果较好;接枝型PLA-PEG荷钆纳米粒性质稳定、T1弛豫率高;接枝型PLA-PEG-PLL荷钆纳米粒粒径优良、性质稳定、活性化学基团多,成像效果最好.结论 利用生物可降解高分子材料可制备肝脏MR分子成像的有效载体,与吸附型纳米粒相比,接枝型PLA-PEG-PLL荷钆纳米粒的优势更加明显.
Objective To synthesize the novel gadolinium-based nanocarriers used for the MR molecular imaging of the liver using four biocompatible materials with different methods, and to probe their properties. Methods Four nanocarriers including solid lipid nano- particles {SLN), poly (lactic acid)-poly (ethylene glycol) (PLA-PEGInanoparticles, and the PLA-PEG-polylysine (PLL) nanopar- ticles using solvent emulsion evaporation method, improved solvent diffusion method, self-assembly method and chemical synthesis method. The physicochemical properties of nanocomplexes were measured by atomic force microscopy (AFM) and photon correla- tion spectroscopy (PCS). The imaging efficiency of those nanocarriers were evaluated through the MRI. Results The mean size of SLN, PLA-PEG nanoparticles (adsorption type), PLA PEG nanoparticles (graft type) and PLA-PEG-PLL nanoparticles (graft type) was(196.1±2.01) nm,(187.9±2.30) nm, (265.9±6.7) nm and (69.8±5.3) nm respectively, while their zeta potential was (17. 12±0.61) mV,(-12. 36±3.58) mV, [-18.71 ±2.3) mV and {23. 03±4.6) my. They also exhibted well biodistribution and high plasma stability. The synthezied methods of adsorption type SLN and the PLA-PEG nanoparticles showing well ima- ging efficiency were simple. The PLA-PEG nanoparticles (graft type) had high steability and T1 relaxivity. And the PLA-PEG-PLL nanoparticles (graft type) exhibted small diameters, high steability and imaging efficiency with more active groups. Conclusion The nanocarriers loaded the gadolinium for the MR molecular imaging can be synthesized by using the biocompatible materials.Compared to the adsorption type nanoparticles, the graft type PLA-PEG-PLL nanoparticles exhibites more advances.