A dual-delivery system of pH-responsive chitosan-functionalized mesoporous silica nanoparticles bearing BMP-2 and dexamethasone for enhanced bone regeneration
A dual-delivery system of pH-responsive chitosan-functionalized mesoporous silica nanoparticles bearing BMP-2 and dexamethasone for enhanced bone regeneration
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带有 BMP-2 和地塞米松的 pH 响应性壳聚糖功能化介孔二氧化硅纳米粒子的双重递送系统，用于增强骨再生
DOI：
10.1039/c4tb01897d
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发表时间：
2015-01-01
影响因子：
7
通讯作者：
Liu, Changsheng
中科院分区：
文献类型：
--
作者：
Gan, Qi;Zhu, Jiaoyang;Liu, Changsheng
骨形态发生蛋白-2 (BMP-2) 被认为是诱导成骨细胞分化和加速骨再生的最有效和最广泛使用的生长因子之一。适当剂量的地塞米松（Dex）可以增强BMP-2诱导的成骨细胞分化。为了加强这种协同骨诱导效应，制备了 pH 响应性壳聚糖功能化介孔二氧化硅纳米颗粒 (chi-MSN) 组合，用于 BMP-2 和 Dex 的双重递送。 MSNs采用CTAB模板溶胶-凝胶法制备，并通过缩水甘油氧基丙基三甲氧基硅烷(GPTMS)的交联进一步涂覆壳聚糖。小的 Dex 被封装在介孔中，大的 BMP-2 被纳入壳聚糖涂层中。这些chi-MSN可以快速释放生物活性形式的BMP-2，然后可以被有效地内吞，并进一步实现Dex随着pH值降低而控制释放到细胞内/细胞内。通过BMP-2和Dex在细胞内外的协同作用，这种双重混合递送系统可以在体外和体内显着刺激成骨细胞分化和骨再生。总之，这种成骨蛋白递送的双重递送策略可以通过保留生物活性和优化药物/蛋白质的释放模式来增强临床结果。
Bone morphogenetic protein-2 (BMP-2) is considered one of the most effective and extensively used growth factors to induce osteoblast differentiation and accelerate bone regeneration. Dexamethasone (Dex) with suitable dosage can enhance BMP-2-induced osteoblast differentiation. To strengthen this synergistic osteoinductive effect, a pH-responsive chitosan-functionalized mesoporous silica nanoparticle (chi-MSN) ensemble was fabricated for dual-delivery of BMP-2 and Dex. The MSNs are prepared by a CTAB-templated sol-gel method, and further coated by chitosan via the crosslinking of glycidoxypropyltrimethoxysilane (GPTMS). The small Dex is encapsulated in the mesopores and the large BMP-2 is incorporated into the chitosan coating. These chi-MSNs can quickly release BMP-2 in a bioactive form and can then be efficiently endocytosed and further realize a controlled release of Dex with the decreased pH value into/in cells. With the synergistic action of BMP-2 and Dex outside and inside the cell, this dual hybrid delivery system can significantly stimulate osteoblast differentiation and bone regeneration in vitro and in vivo. Together, this dual-delivery strategy for osteogenic protein delivery may enhance clinical outcomes by retaining the bioactivity and optimizing the release mode of the drug/protein.