Pan Jie, Feng Si-Shen
Division of Bioengineering, National University of Singapore, Block E3A, #04-15, 7 Engineering Drive 1, Singapore 117574, Singapore.
Biomaterials. 2009 Feb;30(6):1176-83. doi: 10.1016/j.biomaterials.2008.10.039. Epub 2008 Dec 4.
We developed a new strategy to prepare folate-decorated nanoparticles of biodegradable polymers for Quantum dots (QDs) formulation for targeted and sustained imaging for cancer diagnosis at its early stage. Poly(lactide)-vitamin E TPGS (PLA-TPGS) copolymer and vitamin E TPGS-carboxyl (TPGS-COOH) copolymer were synthesized. Their blend at various weight ratio was used to prepare folate-decorated nanoparticles (NPs) for QDs formulation to improve their imaging effects and reduce their side effects. The TPGS-COOH on the NP surface was designed to conjugate folate-NH(2) with advantage to make the targeting effect adjustable. The size of such NPs was found in the range of 280-300nm. In vitro cellular uptakes of such NPs were investigated with confocal laser scanning microscopy (CLSM), which demonstrated much higher internalization of the folate-decorated QDs-loaded PLA-TPGS/TPGS-COOH NPs by MCF-7 breast cancer cells which are of over-expression of folate receptors than the cellular uptake by NIH 3T3 fibroblast cells which are of low expression of folate receptors. Compared with the free QDs, the QDs formulated in the PLA-TPGS/TPGS-COOH NPs showed lower in vitro cytotoxicity for both of MCF-7 cells and NIH 3T3 cells. Additionally, our findings indicated that under same conditions, cytotoxicity of QDs formulated in the PLA-TPGS/TPGS-COOH NPs is lower for normal cells such as NIH 3T3 cells than that for breast cancer such as MCF-7 breast cancer cells due to folate targeting effect. Targeted imaging by QDs formulated in folate-decorated PLA-TPGS/TPGS-COOH nanoparticles with better effects and less side effects is feasible.
我们开发了一种新策略，用于制备叶酸修饰的可生物降解聚合物纳米颗粒，用于量子点（QD）制剂，以实现癌症早期诊断的靶向和持续成像。合成了聚（丙交酯）-维生素E TPGS（PLA-TPGS）共聚物和维生素E TPGS-羧基（TPGS-COOH）共聚物。将它们以不同重量比混合，用于制备叶酸修饰的纳米颗粒（NP），用于量子点制剂，以提高其成像效果并减少副作用。NP表面的TPGS-COOH被设计用于与叶酸-NH(2)共轭，有利于使靶向效果可调节。发现此类NP的尺寸在280-300nm范围内。用共聚焦激光扫描显微镜（CLSM）研究了此类NP的体外细胞摄取，结果表明，叶酸修饰的负载量子点的PLA-TPGS/TPGS-COOH NP被叶酸受体过表达的MCF-7乳腺癌细胞内化的程度远高于叶酸受体低表达的NIH 3T3成纤维细胞的细胞摄取。与游离量子点相比，PLA-TPGS/TPGS-COOH NP中配制的量子点对MCF-7细胞和NIH 3T3细胞均表现出较低的体外细胞毒性。此外，我们的研究结果表明，在相同条件下，由于叶酸靶向作用，PLA-TPGS/TPGS-COOH NP中配制的量子点对NIH 3T3等正常细胞的细胞毒性低于MCF-7乳腺癌等乳腺癌细胞。用叶酸修饰的PLA-TPGS/TPGS-COOH纳米颗粒配制的量子点进行靶向成像，效果更好，副作用更少，是可行的。
