具有骨诱导特性的治疗性非磷脂脂质体纳米载体促进骨形成的设计与表征,ACS Nano

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具有骨诱导特性的治疗性非磷脂脂质体纳米载体促进骨形成的设计与表征
ACS Nano ( IF 15.8 ) Pub Date : 2017-08-11 00:00:00 , DOI: 10.1021/acsnano.7b02702
Zhong-Kai Cui ₁ , Soyon Kim ₂ , Jessalyn J. Baljon ₂ , Mahmoudreza Doroudgar ₃ , Michel Lafleur ₃ , Benjamin M. Wu _{1,

2} , Tara Aghaloo ₄ , Min Lee _{1,

2}

Affiliation

甾体是最近开发的由单链两亲物和高固醇含量形成的非磷脂脂质体的类型。尽管与常规的磷脂脂质体相比，甾体的稳定性大大提高，但目前的甾体生物材料并不是真正的生物活性物质，也没有内在的治疗作用。这项研究的目的是通过有效选择甾醇（一种甾体成分）来开发一种具有骨诱导特性的甾体制剂。氧固醇是胆固醇的氧化衍生物，已知会刺激成骨和骨形成。因此，20S-羟基胆固醇（Oxy）是最有效的骨再生氧固醇之一，被认为是与单链两亲物，即硬脂胺（SA）形成流体层状相的有前途的候选分子。第一的，通过研究SA / Oxy混合物的相行为来确定最佳组成。接下来，评估了优化的SA / Oxy脂质体促进骨髓基质细胞成骨分化的能力。在水凝胶环境中进行体外。此外，我们用小鼠临界大小的颅骨缺损模型探索了成骨性氧固醇甾体在体内的作用。我们的结果表明，SA / Oxy脂质体可在体外诱导成骨分化并增强颅盖愈合，而无需递送其他治疗剂，这表明它们具有内在的成骨潜能。这项研究提出了一种有希望的具有骨诱导特性的非磷脂脂质体平台，用于递送小分子药物和/或其他治疗基因，以增强骨骼的形成。

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Design and Characterization of a Therapeutic Non-phospholipid Liposomal Nanocarrier with Osteoinductive Characteristics To Promote Bone Formation

Sterosomes are recently developed types of non-phospholipid liposomes formed from single-chain amphiphiles and high content of sterols. Although sterosomes presented significantly increased stability compared to conventional phospholipid liposomes, current sterosome biomaterials are not truly bioactive and have no intrinsic therapeutic effects. The purpose of this study was to develop a sterosome formulation with osteoinductive properties by an effective selection of sterol, one of the sterosome components. Oxysterols are oxidized derivatives of cholesterol and are known to stimulate osteogenesis and bone formation. Thus, 20S-hydroxycholesterol (Oxy), one of the most potent oxysterols for bone regeneration, was examined as a promising candidate molecule to form fluid lamellar phases with a single-chain amphiphile, namely, stearylamine (SA). First, the optimal composition was identified by investigating the phase behavior of SA/Oxy mixtures. Next, the capacity of the optimized SA/Oxy sterosomes to promote osteogenic differentiation of bone marrow stromal cells was assessed in vitro in a hydrogel environment. Furthermore, we explored the effects of osteogenic oxysterol sterosomes in vivo with the mouse critical-sized calvarial defect model. Our results showed that SA/Oxy sterosomes induced osteogenic differentiation in vitro and enhanced calvarial healing without delivery of additional therapeutic agents, indicating their intrinsic bone-forming potential. This study suggests a promising non-phospholipid liposomal platform with osteoinductive properties for delivery of small molecular drugs and/or other therapeutic genes for enhanced bone formation.

更新日期：2017-08-12

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