RGD修饰树枝状高分子PAMAM药物靶向传输实验研究

Modification of Polyamidoamine Dendrimer with RGD for Targeted Drug Delivery

制备了RGD靶向修饰的聚酰胺-胺(PAMAM)树枝状聚合物,以阿霉素为药物模型研究了载体的载药性能、体外释放行为及对Hela细胞的毒性.利用激光共聚焦显微镜观察了Hela细胞对药物和材料的摄取行为.结果显示,载体具有良好的生物相容性,Hela细胞对PAMAM-Ac-FITC-RGD的摄取效率≥95%,而对PA-MAM-Ac-FITC的摄取效率<40%,293T细胞对两种材料的摄取效率均低于30%.阿霉素可以通过物理包埋的方法固定,其释放受pH、离子强度等因素的影响较大.共聚焦结果显示,载体可以在较短的时间内携带药物进入Hela细胞.RGD修饰PAMAM使载体获得了靶向性,提高了药物传输效率.

The nano targeting carrier was synthesized by targeting agent RGD conjugated to modified ployamidoamine dendirmer（PAMAM-Ac-FITC-RGD）,the drug loading,release and cytotoxicity to Hela cells were studied with doxorubicin（DOX） as drug modle in vitro.Hela cells uptake of DOX and drug loaded carrier was also observed using confocal microscopy.The results indicated that PAMAM-Ac-FITC-RGD had good biocompatibility.The uptake efficiency of PAMAM-Ac-FITC-RGD（≥95%） by Hela cells was two fold higher than that of PAMAM-Ac-FITC（40%）,and more than threefold higher than the uptake of two conjugates by 293T cells（30%）.DOX can encapsulated to PAMAM-Ac-FITC-RGD,and ion concentration,pH and temperature could affect the release of DOX.The results of confocal microscopy showed that the carrier could facilitate drug to Hela cells in a short time.The modification of RGD to PAMAM make the carrer get targeting capability and improve its drug delivery efficiency.