Development and evaluation of novel tumor-targeting paclitaxel-loaded nano-carriers for ovarian cancer treatment: in vitro and in vivo.
Development and evaluation of novel tumor-targeting paclitaxel-loaded nano-carriers for ovarian cancer treatment: in vitro and in vivo.
复制标题
用于卵巢癌治疗的新型肿瘤靶向紫杉醇纳米载体的开发和评估：体外和体内。
DOI：
10.1186/s13046-018-0700-z
复制
发表时间：
2018-02-26
期刊：
影响因子：
--
通讯作者：
Song K
中科院分区：
文献类型：
--
作者：
Yao S;Li L;Su XT;Wang K;Lu ZJ;Yuan CZ;Feng JB;Yan S;Kong BH;Song K
卵巢癌是女性最主要的死亡原因，也是女性第三常见的妇科恶性肿瘤。传统的化疗方法不可避免地存在肿瘤靶向性不强、毒性大、疗效差等缺点。为了克服这些缺点，我们制备了一种新型的纳米载体给药系统，以提高抗肿瘤的效率。用透射电子显微镜、差示扫描量热仪对纳米载体进行了体外表征。用四甲基偶氮唑盐比色法测定细胞存活率。RT-PCR法检测Farα在三种卵巢癌细胞系中的表达。体外释药试验和摄取试验。体内药代动力学和药物分布研究采用高效液相色谱方法进行验证。通过体内抑瘤率评价FA-NP的增强抗肿瘤作用。成功制备了紫杉醇纳米粒(PTX-PEGLA-NP和PTX-PEGLA-FA-NP)，药物释放研究表明，纳米粒的累积释药速率明显低于游离PTX组。药代动力学研究表明，两种NP组的消除相均明显长于PTX组。药物在不同组织中的分布显示，PTX组的达峰时间为2小时，两种NP组的达峰时间为6小时。这些结果证实了两种纳米载体都具有良好的缓释效果。更重要的是，我们证实了PTX-PEGLA-FA-NP在体外被SK-OV-3细胞摄取的能力高于PTX-PEGLA-NP和游离PTX。荷瘤小鼠体内的药物分布研究表明，PTX-PEGLA-FA-NP组肿瘤组织中的PTX浓度是其他两组的3倍。SK-OV-3细胞摄取PTX-PEGLA-FA-NP的能力明显高于PTX-PEGLA-NP和游离PTX。最后，基于PTX-PEGLA-FA-NP的缓释效应和肿瘤靶向性，细胞毒性试验表明PTX-PEGLA-FA-NP对SK-OV-3细胞的毒性明显高于对照组。PTX-PEGLA-FA-NP组对荷瘤小鼠的抑瘤率约为对照组的1.5倍。体外和体内实验均证实了PTX-PEG-PLA-FA-NP的肿瘤靶向性和抗肿瘤活性。我们成功研制了卵巢癌靶向纳米载体给药系统，该系统具有良好的卵巢癌靶向性和抗肿瘤作用，有望成为卵巢癌患者的一种新的治疗策略。本文的在线版本(10.1186/s13046-0180700-z)包含补充材料，可供授权用户使用。
Ovarian cancer is the most leading cause of death and the third most common gynecologic malignancy in women. Traditional chemotherapy has inevitable drawbacks of nonspecific tumor targeting, high toxicity, and poor therapeutic efficiency. In order to overcome such shortcomings, we prepared a novel nano-carrier drug-delivery system to enhance the anti-tumor efficiency. In vitro characterizations of nano-carriers were determined by TEM, DLS. Cell viability was measured by MTT method. RT-PCR was performed to measure the expression of FARα in three ovarian cancer cell lines. The drug-release study and the uptaken study were measured in vitro. The pharmacokinetic and the drug distribution study were verified by HPLC methods in vivo. The enhanced anti-tumor efficiency of FA-NP was evaluated by the tumor inhibitory rate in vivo. Paclitaxel (PTX)-loaded nanoparticles (NPs) (PTX-PEG-PLA-NP and PTX-PEG-PLA-FA-NP) were prepared successfully, and the drug-release study showed that the cumulative release rates of NP groups were much less than free PTX group. The pharmacokinetic study showed that the elimination phase of two kinds of NP groups were much longer than that of PTX group. The drug distribution in different tissues showed that the peak-reach time was 2 h in the PTX group and 6 h in both NP groups. All of these results confirmed the excellent slow-release effects of both kinds of nano-carriers. More importantly, we confirmed that PTX-PEG-PLA-FA-NP had greater uptake by SK-OV-3 cells than PTX-PEG-PLA-NP and free PTX in vitro. A drug-distribution study of tumor-bearing mice demonstrated that the PTX concentration of tumor tissues in the PTX-PEG-PLA-FA-NP group was 3 times higher than the other two groups. PTX-PEG-PLA-FA-NP was uptaken much more by SK-OV-3 cells than PTX-PEG-PLA-NP and free PTX. Eventually, based on the slow-release effect and tumor-targeting characteristics of PTX-PEG-PLA-FA-NP, a cytotoxicity test indicated that PTX-PEG-PLA-FA-NP was much more toxic to SK-OV-3 cells than the controls. The tumor inhibitory rate in the PTX-PEG-PLA-FA-NP group of tumor-bearing mice was about 1.5 times higher than the controls. The tumor targeting and anti-tumor efficiency of PTX-PEG-PLA-FA-NP were confirmed both in vitro and in vivo. We developed an ovarian cancer targeting nano-carrier drug delivery system successfully, which showed perfect ovarian cancer targeting and anti-tumor effect, thus have the potential to be a new therapy strategy for ovarian cancer patients. The online version of this article (10.1186/s13046-018-0700-z) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
5.2
作者：
Li, Zhao;Sun, Liping;Kong, Beihua
通讯作者：
Kong, Beihua
DOI：
10.1016/j.jconrel.2013.09.013
发表时间：
2013-12-28
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Ernsting MJ;Murakami M;Roy A;Li SD
通讯作者：
Li SD
影响因子：
64.8
作者：
Sengupta, S;Eavarone, D;Sasisekharan, R
通讯作者：
Sasisekharan, R
影响因子：
254.7
作者：
Siegel, Rebecca;Ma, Jiemin;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
影响因子：
8
作者：
Wang B;Jiang W;Yan H;Zhang X;Yang L;Deng L;Singh GK;Pan J
通讯作者：
Pan J