Transferrin-Modified Doxorubicin-Loaded Biodegradable Nanoparticles Exhibit Enhanced Efficacy in Treating Brain Glioma-Bearing Rats
Transferrin-Modified Doxorubicin-Loaded Biodegradable Nanoparticles Exhibit Enhanced Efficacy in Treating Brain Glioma-Bearing Rats
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转铁蛋白修饰的负载阿霉素的可生物降解纳米颗粒在治疗患有脑胶质瘤的大鼠中表现出增强的功效
DOI：
10.1089/cbr.2013.1480
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发表时间：
2013-11-01
影响因子：
3.4
通讯作者：
Lan, Qing
中科院分区：
文献类型：
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作者：
Liu, Guodong;Mao, Jinning;Lan, Qing
多柔比星（Dox）广泛用于实体瘤的治疗，但其在胶质瘤的临床应用有限。在本研究中，我们开发了一种新型的纳米级药物释放系统，采用可生物降解的纳米粒子（NP）作为载体负载阿霉素。将转铁蛋白（Transferrin，Tf）偶联到NP的表面，使NP特异性靶向胶质瘤。采用沉淀-溶剂挥发法制备了Tf-NP-Dox纳米粒，并对其粒径、载药量、包封率和表面Tf值进行了表征。采用CCK-8法评价其体外抗肿瘤活性。通过HPLC测定评价跨膜转运。采用大鼠C6胶质瘤颅内种植模型评价其体内抑瘤效果。Tf-NP-Dox的平均粒径为100 nm，表面约有32个Tf分子。DLC为4.4%。CCK-8法显示Tf-NP-Dox对C6胶质瘤细胞的杀伤作用明显强于NP-Dox或Dox。高效液相色谱分析表明，Tf-NP-Dox能高效地将Dox转运至C6细胞内。在体内实验中，Tf-NP-Dox能将Dox转运至肿瘤内，其抑瘤率和存活率均高于NP-Dox和Dox。以上结果表明，Tf-NP-Dox在体内外均具有较好的抗胶质瘤作用，是一种潜在的胶质瘤化疗纳米给药系统。
Doxorubicin (Dox) is widely used for the treatment of solid tumors but its clinical utility on glioma is limited. In this study, we developed a novel nano-scale drug delivery system employing biodegradable nanoparticle (NP) as carriers to load Dox. Transferrin (Tf) was conjugated to the surface of NP to specifically target the NP to glioma. Tf-NP-Dox was prepared via emulsification-solvent evaporation method, and characterized for the size, Drug loading capacity (DLC), entrapment efficiency, and Tf number on the surface. The antitumor efficiency in vitro was evaluated via CCK-8 assay. The transmembrane transportation was evaluated via HPLC assay. The antitumor efficiency in vivo was assessed in C6 glioma intracranial implant rat model. The average diameter of Tf-NP-Dox was 100nm with approximate to 32 Tf molecules on the surface. DLC was 4.4%. CCK-8 assay demonstrated much stronger cytotoxicity of Tf-NP-Dox to C6 glioma cells compared to NP-Dox or Dox. HPLC assay showed that Tf-NP-Dox transported Dox into C6 cells with high efficiency. In vivo, Tf-NP-Dox could transport Dox into tumors compare to contralateral part, with tumor inhibitory ratio and survival higher than NP-Dox or Dox. Taken together, our results suggest that Tf-NP-Dox exhibits better therapeutic effects against glioma both in vitro and in vivo, and is a potential nano-scale drug delivery system for glioma chemotherapy.