RGD肽修饰病毒样颗粒靶向递送阿霉素的初步研究

Preparation of virus-like particles modified with RGD peptide and targeted delivery of doxorubicin

目的探究以乙肝病毒样颗粒(HBc-RGD-VLPs)作为递送抗癌药物DOX载体,制备靶向纳米复合物针对乳腺癌4T1细胞的生物学影响。方法用制备的乙肝假病毒颗粒包封DOX,形成靶向纳米复合物HBc-RGD-VLPs/DOX。通过透射电镜及粒度仪检测颗粒的均一度及形态,并将其应用到4T1细胞进行体外生物活性探究。结果通过透射电镜检测靶向纳米复合物HBc-RGD-VLPs/DOX的结构完整,形态均一,为规则的球形颗粒,粒径分布为30~35 nm。体外细胞实验表明靶向载体HBc-RGD-VLPs的安全性较好,细胞存活率达到80%以上,包封后的HBc-RGD-VLPs/DOX对4T1细胞的生长有明显抑制效果,其针对4T1肿瘤细胞的半数有效浓度(IC50)为1.445μg/ml。荧光显微镜观察到HBc-RGD-VLP/DOX相对于游离DOX可特异性靶向至肿瘤细胞。结论靶向载体HBc-RGD-VLPs的安全性较好,HBc-RGD-VLPs/DOX对肿瘤细胞显示出较好的增殖抑制效果及一定的肿瘤靶向性。

Objective To explore the biological effects of the targeted nanocomposite on breast cancer 4T1 cells with hepatitis B virus-like particles(HBc-RGD-VLPs)as a carrier for the delivery of anti-cancer drugs,and to provide a new theoretical basis for reducing the toxicity of doxorubicin(DOX)anti-tumor drugs and changing the path of administration.Methods The hepatitis B pseudoviral particles prepared in the early stage of this laboratory enveloped DOX to form a target nanocomposite HBc-RGD-VLPs/DOX.The homogeneity and morphology of particles were detected by transmission electron microscopy and granular size analyzer,and applied to 4T1 cells for in vitro bioactivity exploration.Results The structure of the target nanocomposite HBc-RGD-VLPs/DOX was detected by means of a transmission electron microscope,in a homogenous form,and the particle size distribution was 30-35 nm.In vitro cell experiments showed that the safety of target vector HBc-RGD-VLPs was better,the cell survival rate was more than 80%,and the HBc-RGD-VLPs/DOX after encapsulation had a significant inhibitory effect on the growth of 4T1 cells,and the effective inhibitory concentration(IC50)for half of 4T1 tumor cells was 1.445 g/ml.Fluorescence microscopy showed that HBc-RGD-VLP/DOX can be specifically targeted to tumor cells relative to the isolated DOX.Conclusions The safety of target vector HBc-RGD-VLPs is better,HBc-RGD-VLPs/DOX showed good proliferation inhibitory effect and certain tumor-targeting effect on tumor cells.