Facile Preparation of Paclitaxel Loaded Silk Fibroin Nanoparticles for Enhanced Antitumor Efficacy by Locoregional Drug Delivery
Facile Preparation of Paclitaxel Loaded Silk Fibroin Nanoparticles for Enhanced Antitumor Efficacy by Locoregional Drug Delivery
复制标题
轻松制备负载紫杉醇的丝素蛋白纳米颗粒，通过局部药物递送增强抗肿瘤功效。
DOI：
10.1021/am403992b
复制
发表时间：
2013-12-11
影响因子：
9.5
通讯作者：
Liu, Baorui
中科院分区：
文献类型：
--
作者：
Wu, Puyuan;Liu, Qin;Liu, Baorui
无毒、安全的材料和制备方法是设计用于未来临床应用的纳米颗粒（NPs）时最重要的因素之一。在这里，我们报告了一种新的和简单的方法，将抗癌药物紫杉醇（PTX）封装到丝素蛋白（SF），一种生物相容性和可生物降解的天然聚合物，不添加任何有毒的有机溶剂，表面活性剂或其他有毒试剂。通过丝素蛋白（SF）的自组装，在水溶液中制备了直径为130 nm的紫杉醇负载丝素蛋白纳米粒（PTX-SF-NPs）。在细胞摄取实验中，两种人胃癌细胞系BGC-823和SGC-7901有效地摄取了香豆素-6负载的SF NPs。体外细胞毒性研究表明，PTX掺入PTX-SF-NPs后保持了其药理活性，而SF对细胞无细胞毒性。在胃癌裸鼠移植瘤模型上评价PTX-SF-NPs的体内抗肿瘤作用。我们发现，与全身给药相比，PTX-SF-NP的局部区域递送通过延迟肿瘤生长和降低肿瘤重量表现出上级抗肿瘤功效。此外，纳米粒处理组小鼠的器官未显示出明显的毒性，表明SF纳米粒在体内是安全的。这些结果表明，SF NPs是有前途的药物递送载体，并且SF NPs的局部递送可能是潜在的未来临床癌症治疗方案。
Non-toxic, safe materials and preparation methods are among the most important factors when designing nanoparticles (NPs) for future clinical application. Here we report a novel and facile method encapsulating anticancer drug paclitaxel (PTX) into silk fibroin (SF), a biocompatible and biodegradable natural polymer, without adding any toxic organic solvents, surfactants or other toxic agents. The paclitaxel loaded silk fibroin nanoparticles (PTX-SF-NPs) with a diameter of 130 nm were formed in an aqueous solution at room temperature by self-assembling of SF protein, which demonstrated mainly silk I conformation in the NPs. In cellular uptake experiments, coumarin-6 loaded SF NPs were taken up efficiently by two human gastric cancer cell lines BGC-823 and SGC-7901. In vitro cytotoxicity studies demonstrated that PTX kept its pharmacological activity when incorporating into PTX-SF-NPs, while SF showed no cytotoxicity to cells. The in vivo antitumor effects of PTX-SF-NPs were evaluated on gastric cancer nude mice exnograft model. We found that locoregional delivery of PTX-SF-NPs demonstrated superior antitumor efficacy by delaying tumor growth and reducing tumor weights compared with systemic administration. Furthermore, the organs of mice in NP treated groups didn't show obvious toxicity, indicating the in vivo safety of SF NPs. These results suggest that SF NPs are promising drug delivery carriers, and locoregional delivery of SF NPs could be a potential future clinical cancer treatment regimen.