Versatile Nanocarrier Based on Functionalized Mesoporous Silica Nanoparticles to Codeliver Osteogenic Gene and Drug for Enhanced Osteodifferentiation
Versatile Nanocarrier Based on Functionalized Mesoporous Silica Nanoparticles to Codeliver Osteogenic Gene and Drug for Enhanced Osteodifferentiation
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基于功能化介孔二氧化硅纳米颗粒的多功能纳米载体可传递成骨基因和增强骨分化的药物
DOI：
10.1021/acsbiomaterials.8b01110
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发表时间：
2019
影响因子：
--
通讯作者：
He Chuanglong
中科院分区：
文献类型：
--
作者：
Zhou Xiaojun;Zhang Qianqian;Chen Liang;Nie Wei;Wang Weizhong;Wang Hongsheng;Mo Xiumei;He Chuanglong
为了增强对干细胞成骨分化的刺激作用，具有协同生物活性的双因素组合被认为是最有效和最有力的策略。本研究首先合成了具有不同分子量PEI嵌段的聚赖氨酸修饰的聚乙烯亚胺（PEI-PLL）共聚物，并对其细胞毒性和基因转染效率进行了评估，结果表明，合成的共聚物PEI-PLL-25k（使用25 kDa PEI合成）表现出较低的细胞毒性和较高的细胞毒性。 体外转染效率高于商业 PEI-25k (Mw= 25 kDa)。为了有效地负载和递送质粒DNA和成骨药物地塞米松（DEX），将PEI-PLL-25k共聚物和精氨酸-甘氨酸-天冬氨酸（RGD）肽先后锚定在介孔二氧化硅纳米粒子（MSNs）的表面，构建双因子递送系统，使得DNA和DEX负载在介孔二氧化硅纳米颗粒（MSNs）的表面吸附。 MSN 的中孔。通过各种技术成功地表征了 PEI-PLL-25k 共聚物和 RGD 对纳米颗粒的改性。体外细胞活力测定和细胞骨架观察证明，表面具有 RGD 缀合的功能化 MSN 显示出良好的细胞相容性。双因子递送系统可以快速释放质粒DNA（pDNA），同时持续释放DEX。当与携带骨形态发生蛋白2（BMP-2）pDNA的载体一起培养时，转染的骨髓间充质干细胞（BMSC）能够表达BMP-2蛋白。通过同时递送 DEX 和 BMP-2 基因，这种双因子递送系统可以显着增强 BMSC 的成骨分化水平，碱性磷酸酶 (ALP) 活性、骨相关基因表达和钙沉积的体外结果证明了这一点。因此，用于成骨基因和药物共同递送的多功能功能化MSNs纳米载体可能被认为是一种有前途的双重递送系统，可以协同增强干细胞的成骨效果。
To achieve enhanced stimulatory effects on the osteogenic differentiation of stem cells, the combination of dual factors with synergistic bioactivity has been regarded as the most effective and powerful strategy. In this study, polylysine-modified polyethylenimine (PEI-PLL) copolymers with various molecular weight PEI blocks were first synthesized and evaluated focusing on their cytotoxicity and gene transfection efficiency, and the results demonstrated that the synthesized copolymer PEI-PLL-25k (synthesized using 25 kDa PEI) exhibited lower cytotoxicity and higherin vitrotransfection efficiency than commercial PEI-25k (Mw= 25 kDa). In order to effectively load and deliver plasmid DNA and osteogenic drug dexamethasone (DEX), PEI-PLL-25k copolymer and arginine-glycine-aspartate (RGD) peptide were successively anchored onto the surface of mesoporous silica nanoparticles (MSNs) to construct the dual-factor delivery system, which allows the surface adsorption of DNA and DEX loading in the mesopores of MSNs. The modification of PEI-PLL-25k copolymer and RGD on nanoparticles was successfully characterized by various techniques. The functionalized MSNs with RGD conjugation on the surface showed good cytocompatibility as evidenced byin vitrocell viability assays and cytoskeleton observation. The dual-factor delivery system could quickly release plasmid DNA (pDNA), while releasing DEX in a sustained manner. When cultured with the vector bearing bone morphogenetic protein-2 (BMP-2) pDNA, the transfected bone mesenchymal stem cells (BMSCs) were capable of expressing BMP-2 protein. With the simultaneous delivery of DEX and the BMP-2 gene, this dual-factor delivery system could significantly enhance the level of osteogenic differentiation of BMSCs, as demonstrated byin vitroresults of alkaline phosphatase (ALP) activity, expression of osteo-related genes, and calcium deposition. Therefore, the versatile functionalized MSNs nanocarrier for codelivery of osteogenic gene and drug may be considered as a promising dual-delivery system to synergistically enhance the osteogenic outcomes of stem cells.