Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China; University of Chinese Academy of Sciences, Beijing 100039, China.
Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
Carbohydr Polym. 2018 Dec 1;201:246-256. doi: 10.1016/j.carbpol.2018.08.063. Epub 2018 Aug 19.
In gene therapy, the stability of gene delivery system is essential during the systemic circulation. To improve the stability of PEI/DNA complexes, sodium alginate (Alg) was chosen as the optimal shielding material from four different polysaccharides. Then Alg/PEI/DNA complexes were further crosslinked by calcium ions (Ca) to form Ca/(Alg/PEI/DNA) nanoparticles. Compared to PEI/DNA complexes and Alg/PEI/DNA complexes, Ca/(Alg/PEI/DNA) nanoparticles exhibited enhanced stability, which was confirmed by the in vitro and in vivo evaluations. Furthermore, the pharmacokinetic study indicated that Ca/(Alg/PEI/DNA) nanoparticles exhibited longer circulation time in blood, which would be beneficial to the enhanced permeability and retention (EPR) effect of nanoparticles and could realize improved nanoparticles accumulation at tumor site. Overall, the Ca/(Alg/PEI/DNA) nanoparticles based on alginate shielding and Ca crosslinking might be a promising platform in gene delivery and tumor treatment.
在基因治疗中，基因传递系统在全身循环过程中的稳定性至关重要。为了提高 PEI/DNA 复合物的稳定性，从四种不同的多糖中选择了海藻酸钠 (Alg) 作为最佳屏蔽材料。然后，通过钙离子 (Ca) 将 Alg/PEI/DNA 复合物进一步交联，形成 Ca/(Alg/PEI/DNA)纳米颗粒。与 PEI/DNA 复合物和 Alg/PEI/DNA 复合物相比，Ca/(Alg/PEI/DNA)纳米颗粒表现出增强的稳定性，这通过体外和体内评估得到了证实。此外，药代动力学研究表明，Ca/(Alg/PEI/DNA)纳米颗粒在血液中的循环时间更长，这有利于纳米颗粒的增强渗透性和保留 (EPR) 效应，并可实现纳米颗粒在肿瘤部位的积累得到改善。总的来说，基于海藻酸钠屏蔽和 Ca 交联的 Ca/(Alg/PEI/DNA)纳米颗粒可能是基因传递和肿瘤治疗的一个有前途的平台。
