Zhang Luzhong, Li Guicai, Gao Ming, Liu Xin, Ji Bing, Hua Ruheng, Zhou Youlang, Yang Yumin
Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, China; Hand Surgery Research Center, Department of Hand Surgery, Affiliated Hospital of Nantong University, Nantong 226001, China.
Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, China.
Colloids Surf B Biointerfaces. 2016 Aug 1;144:81-89. doi: 10.1016/j.colsurfb.2016.03.077. Epub 2016 Apr 2.
Recently, chemotherapy-based polymeric nanoparticles have been extensively investigated for solid tumor treatment. Tumor targeted nanoparticles demonstrated great potential for improved accumulation in the tumor tissue, superior anticancer activity and reduced side effects. Thus, inulin-ibuprofen polymer was synthesized by esterification between inulin and ibuprofen, and RGD targeted epirubicin (EPB) loaded nanoparticles were prepared by the self-assembly of inulin-ibuprofen polymer and in situ encapsulation of EPB. RGD conjugated EPB loaded nanoparticles were characterized by dynamic light scattering (DLS) and transmission electron microscope (TEM). The EPB release from the nanoparticles showed pH-dependent profile and accelerated by the decreased pH value, which would favor the effective drug delivery in vivo. Intracellular uptake analysis suggested that RGD conjugated nanoparticles could be easily internalized by the cancer cells. In vitro cytotoxicity revealed that RGD conjugated EPB loaded nanoparticles exhibited the better antitumor efficacy compared with non-conjugated nanoparticles. More importantly, RGD conjugated EPB loaded nanoparticles showed superior anticancer effects and reduced toxicity than free EPB and non-conjugated nanoparticles by in vivo antitumor activity, EPB biodistribution and histology analysis.
最近，基于化疗的聚合物纳米颗粒已被广泛研究用于实体瘤治疗。肿瘤靶向纳米颗粒在改善肿瘤组织中的积累、增强抗癌活性和减少副作用方面显示出巨大潜力。因此，通过菊粉与布洛芬之间的酯化反应合成了菊粉-布洛芬聚合物，并通过菊粉-布洛芬聚合物的自组装和表柔比星（EPB）的原位包封制备了RGD靶向载药纳米颗粒。通过动态光散射（DLS）和透射电子显微镜（TEM）对RGD偶联的载EPB纳米颗粒进行了表征。纳米颗粒中EPB的释放呈现pH依赖性，随着pH值降低而加速，这有利于体内有效的药物递送。细胞内摄取分析表明，RGD偶联的纳米颗粒能够被癌细胞轻易内化。体外细胞毒性实验表明，与未偶联的纳米颗粒相比，RGD偶联的载EPB纳米颗粒具有更好的抗肿瘤效果。更重要的是，通过体内抗肿瘤活性、EPB生物分布和组织学分析，RGD偶联的载EPB纳米颗粒比游离EPB和未偶联的纳米颗粒显示出更强的抗癌作用和更低的毒性。
