Nanoparticles have been widely applied in diagnosis and therapy due to the high loading of insoluble drug, increased target accumulation and interaction with biological tissues. Recently, severe side effects of nanoparticles have been reported, but the underlying mechanism remains largely unknown. In our study, we aim to understand the safety of paclitaxel （PTX） loaded bovine albumin nanoparticles （BNPs） and active targeted PTX loaded BNPs to normal vital organ or tissue in vivo. The anti-human epidermal growth factor receptor 2 （HER2/neu） peptide mimetic （AHNP） was covalent bound to surface of BNPs （AHNP-BNPs） to exert selected delivery to HER2＋ cells. In HER2＋ tumor xenographs, saline （control）, PTX traditional formula （medium of Cremophor EL-ethanol）, BNPs, and AHNP-BNPs were administrated to evaluate the toxicity. There is no severe neutropenia or anemia with treatment of BNPs and AHNP-BNPs compared with traditional PTX injection. We also evaluated their damage on normal organs, including liver, kidney, spleen, lung and heart to fully estimate the safety of AHNP-BNPs and BNPs delivery systems. We observed similar toxicity in liver and lung in mice treated with BNPs or PTX injection, but decreased liver damage in mice treated with AHNP-BNPs. Further studies are rcouired to confirm our conclusion.
目的对^(131)I-c(RGD)_(2)在原位荷脑胶质瘤动物模型中的靶向定位作用进行研究,以探讨其应用于脑胶质瘤诊断与治疗的可能性。方法采用U87-MG人脑胶质瘤细胞接种在裸鼠右脑尾状核内,建立了原位荷脑胶质瘤动物模型;采用氯氨T法将^(131)I标记c(RGD)_(2),于原位荷脑胶质瘤裸鼠中进行生物分布研究,计算^(131)I-c(RGD)_(2)在脑胶质瘤中的摄取率及肿瘤与正常脑组织摄取率的比值(T/NT)。结果给药后3 h及6 h,肾的摄取均为所有器官中最高;给药后3 h肿瘤未累及的脑组织的摄取率为(0.16±0.10)%ID/g,胶质瘤组织的摄取率为(0.41±0.26)%ID/g,脑胶质瘤中的摄取率显著高于正常脑组织摄取率(P值为0.025);给药后6 h肿瘤未累及的脑组织的摄取率为(0.08±0.04)%ID/g,胶质瘤组织的摄取率为(0.44±0.23)%ID/g,脑胶质瘤中的摄取率亦显著高于正常脑组织摄取率(P值为0.011);给药后3 h T/NT比值为3.36±1.86,给药后6 h T/NT比值增高至5.55±1.75。结论c(RGD)_(2)具有靶向颅内胶质瘤的能力,在胶质瘤的靶向诊断与治疗中具有潜力,但其在脑胶质瘤中的摄取率相对较低,有待于进一步提高。
Hepatocellular carcinoma （HCC） is one of the major causes of death worldwide. Targeted delivery of drugs to tumor cells can be achieved by introduction of a targeting ligand onto the nanocarrier system. Simultaneous delivery of a chemotherapeutic drug and siRNA in one nanocarrier system to the tumor is a promising strategy for cancer treatment. In this study, we prepared cationic liposomes to co-deliver docetaxel （DTX） and small interfering RNA （siRNA）. The liposomes were modified by a hepatocellular carcinoma specific homing peptide, SP94. Serum stability assay demonstrated that liposomes can significantly protect the siRNA against enzymatic degradation in serum. The SP94 modified liposomes showed increased cellular uptake and stronger anti-tumor effect compared with the unmodified liposomes on human HCC cells. The data indicated that the SP94 modified liposomes which co-deliver DTX and siRNA could be used for the targeted therapy of hepatocellular carcinoma.
