Transferrin-modified nanostructured lipid carriers as multifunctional nanomedicine for codelivery of DNA and doxorubicin.
Transferrin-modified nanostructured lipid carriers as multifunctional nanomedicine for codelivery of DNA and doxorubicin.
复制标题
DOI：
10.2147/ijn.s67770
复制
发表时间：
2014
影响因子：
8
通讯作者：
Kong F
中科院分区：
文献类型：
--
作者：
Han Y;Zhang Y;Li D;Chen Y;Sun J;Kong F
由固体和液体脂质组成的纳米脂质载体(NLC)和表面活性剂是潜在的良好的胶体药物载体。本研究的目的是开发表面修饰的NLC作为多功能纳米药物，用于增强型绿色荧光蛋白(PEGFP)和阿霉素(DOX)的共传递。制备了两种不同的纳米载体：pEGFP和DOX负载的NLC和固体脂质纳米粒(SLN)。含有转铁蛋白的配体被用于载体的表面包被。对其平均粒径、Zeta电位和药物包封率进行了评价。用人肺泡腺癌细胞系(A549细胞)进行体外转染率的测定，在荷A549细胞的小鼠模型上进行体内转染率的测定。转铁蛋白修饰的DOX和pEGFP共包裹的NLC(T-NLC)的颗粒尺寸为198 nm，表面电荷为+19 mV。与对照组相比，T-NLC制剂的体外细胞存活率超过80%。与DOX和pEGFP共包裹的SLN相比，T-NLC具有更高的基因转染率和更强的体内抗肿瘤活性。结果表明，T-NLC通过基因治疗与化疗相结合，显著增强了抗肿瘤活性。此外，活性转铁蛋白的涂层还改善了载体对肺癌细胞的靶向性。综上所述，这种新型的基因和药物传递系统为肺癌的治疗提供了一种很有前途的策略。
Nanostructured lipid carriers (NLC), composed of solid and liquid lipids, and surfactants are potentially good colloidal drug carriers. The aim of this study was to develop surface-modified NLC as multifunctional nanomedicine for codelivery of enhanced green fluorescence protein plasmid (pEGFP) and doxorubicin (DOX). Two different nanocarriers: pEGFP- and DOX-loaded NLC, and solid lipid nanoparticles (SLN) were prepared. Transferrin-containing ligands were used for the surface coating of the vectors. Their average size, zeta potential, and drug encapsulation capacity were evaluated. In vitro transfection efficiency of the modified vectors was evaluated in human alveolar adenocarcinoma cell line (A549 cells), and in vivo transfection efficiency of the modified vectors was evaluated in a mouse bearing A549 cells model. Transferrin-modified DOX and pEGFP coencapsulated NLC (T-NLC) has a particle size of 198 nm and a +19 mV surface charge. The in vitro cell viabilities of the T-NLC formulations were over 80% compared with the control. T-NLC displayed remarkably greater gene transfection efficiency and enhanced antitumor activity than DOX- and pEGFP-coencapsulated SLN in vivo. The results demonstrate that T-NLC noticeably enhanced antitumor activity through the combination of gene therapy with chemotherapy. Also coating of active transferrin improved the lung cancer cell-targeting of the carriers. In summary, the novel gene and drug delivery system offers a promising strategy for the treatment of lung cancer.