Polymer-based nanoparticles for chemo/gene-therapy: Evaluation its therapeutic efficacy and toxicity against colorectal carcinoma
Polymer-based nanoparticles for chemo/gene-therapy: Evaluation its therapeutic efficacy and toxicity against colorectal carcinoma
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DOI：
10.1016/j.biopha.2019.109257
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发表时间：
2019-10-01
影响因子：
7.5
通讯作者：
Xiao, HongTao
中科院分区：
文献类型：
--
作者：
Chen, Yan;Li, NingXi;Xiao, HongTao
通过纳米制剂同时递送抗癌药物和基因的联合治疗已被证明是一种优雅而有效的结直肠癌治疗方法。近年来，索拉非尼在结直肠癌（CRC）联合治疗中的研究引起了研究者的关注。在我们前期研究的基础上，色素上皮衍生因子（PEDF）纳米粒在体内外对结直肠癌均有良好的治疗作用。在此，我们设计了一种联合治疗索拉非尼（索拉），一种多激酶抑制剂和PEDF，一种强大的抗血管生成基因，在纳米制剂，旨在增加对CRC的抗肿瘤作用的第一次。采用改进的复乳溶剂挥发法将索拉和PEDF同时包封在PEG-PLGA纳米粒中。所获得的共包封纳米颗粒（索拉@ PEDF-NPs）显示出索拉和PEDF -两者的高包封率，并且表现出均匀的球形形态。索拉和PEDF的释药曲线呈持续性。与非药物纳米颗粒、游离索拉、单药纳米颗粒（索拉-纳米颗粒和PEDF-纳米颗粒）以及索拉-纳米颗粒和等效PEDF-纳米颗粒的混合物（混合物-纳米颗粒）相比，在索拉@ PEDF-纳米颗粒中观察到C26细胞和携带C26的小鼠中最有效的肿瘤生长抑制。更重要的是，根据急性毒性试验，索拉@ PEDF-NP在小鼠中显示出比游离索拉更低的毒性。血清生化分析和治疗期间小鼠体重测定结果显示，索拉@PEDF-NPs无明显毒性。这些数据表明，同时负载多激酶抑制剂和抗血管生成基因的纳米粒可能是临床上治疗大肠癌最有潜力的制剂之一，值得进一步研究。
Combination treatment through simultaneous delivery of anticancer drugs and gene with nano-formulation has been demonstrated to be an elegant and efficient approach for colorectal cancer therapy. Recently, sorafenib being studied in combination therapy in colorectal cancer (CRC) attracted attention of researchers. On the basis of our previous study, pigment epithelium-derived factor (PEDF) loaded nanoparticles showed good effect on CRC in vitro and in vivo. Herein, we designed a combination therapy for sorafenib (Sora), a multi-kinase inhibitor and PEDF, a powerful antiangiogenic gene, in a nano-formulation aimed to increase anti-tumor effect on CRC for the first time. Sora and PEDF were simultaneously encapsulated in PEG-PLGA based nanoparticles by a modified double-emulsion solvent evaporation method. The obtained co-encapsulated nanoparticles (Sora@PEDF-NPs) showed high entrapment efficiency of both Sora and PEDF - and exhibited a uniform spherical morphology. The release profiles of Sora and PEDF were in a sustained manner. The most effective tumor growth inhibition in the C26 cells and C26-bearing mice was observed in the Sora@PEDF-NPs in comparison with none-drug nanoparticles, free Sora, mono-drug nanoparticles (Sora-NPs and PEDF-NPs) and the mixture of Sora-NPs and equivalent PEDF-NPs (Mix-NPs). More importantly, Sora@PEDF-NPs showed lower toxicity than free Sora in mice according to the acute toxicity test. The serologic biochemical analysis and mice body weight during therapeutic period revealed that Sora@PEDF-NPs had no obvious toxicity. All the data demonstrated that the simultaneously loaded nanoparticles with multi-kinase inhibitor and anti-angiogenic gene might be one of the most potential formulations in the treatment of colorectal carcinoma in clinic and worthy of further investigation.