环状RGDs修饰的分子刷型共聚物在成像及药物运输中的应用

Cyclic RGDs Modified Copolymeric Brush for Targeted Cellular Imaging and Drug Delivery

以具有丰富接枝侧链的阴离子型共轭聚合物分子刷PFPANa为材料,通过简单的一步修饰法在聚合物的部分接枝侧链上引入靶向配体分子c(RGDyK),并利用分子刷侧链上未修饰配体分子的羧基负离子与抗癌药物DOX静电结合,制备了基于分子刷型共轭聚合物的靶向细胞成像和载药系统.研究结果表明载药系统对DOX药物的载药量可达13.3 wt%,体外细胞实验研究结果表明该载药系统可实现对肿瘤细胞的靶向选择性成像,并显著促进了肿瘤细胞对DOX药物的摄取,具有良好的抗肿瘤细胞生长效果,显著提高了药物运输效率.

The anionic molecular brush conjugated polyelectrolyte PFPANa with a lot of grafted side chains was used in this work. Considering the special molecule structure and advanced photophysical properties of molecular brush conjugated polymer PFPANa, the single-step modification of the targeted functional molecules peptides including Arg-Gly-Asp in part of side chains of polymer PFPANa through covalent linkage was completed and the targeted brush copolymer PFPARGD was prepared. Then the anti-cancer drug DOX was electrostatically combined to polymer PFPARGD as a result of the abundant negative charged carboxyl groups in the remained side chains, and the final combined system for targeted imaging and drug delivery based molecular brush conjugated polymer was prepared. The UV-Vis absorption spectra and the zeta potentials of the polymer before and after modified were measured and the results proved the successfully covalent bonding of cyclic peptides c（RGDyK） to the grafted side chains of PFPANa. The experimental results of the fluorescence quenching assay by the positively charged anti-cancer drug DOX showed that the drug delivery system could still loading about 13.3 wt% DOX even after modification. The cell culture experiments in vitro and the MTT assay in NIH-3T3 cells showed no significant toxicity of the modified polymer PFPARGD. For targeted imaging, the modified polymer PFPARGD was added in both cancer cell and normal cell culture experiments and the laser scanning confocal microscopy images showed that the introduction of targeting ligand c（RGDyK） to the polymer helped to achieve selective recognition of the tumor cells and targeted imaging. The results of flow cytometry showed that the drug delivery system significantly promoted cellular uptake of drug and also showed a good effect of anti-tumor cell growth. This work would provide a new simple strategy for the brush copolymers application in biological drug delivery and molecular imaging of multi-functional system in the future.