Grup d'Enginyeria de Materials (GEMAT), Institut Quimic de Sarrià, Universidad Ramon Llul, Barcelona, 08017, Spain.
Adv Healthc Mater. 2015 Jan 28;4(2):271-80. doi: 10.1002/adhm.201400235. Epub 2014 Aug 11.
Of all the much hyped and pricy cancer drugs, the benefits from the promising siRNA small molecule drugs are limited. Lack of efficient delivery vehicles that would release the drug locally, protect it from degradation, and ensure high transfection efficiency, precludes it from fulfilling its full potential. This work presents a novel platform for local and sustained delivery of siRNA with high transfection efficiencies both in vitro and in vivo in a breast cancer mice model. siRNA protection and high transfection efficiency are enabled by their encapsulation in oligopeptide-terminated poly(β-aminoester) (pBAE) nanoparticles. Sustained delivery of the siRNA is achieved by the enhanced stability of the nanoparticles when embedded in a hydrogel scaffold based on polyamidoamine (PAMAM) dendrimer cross-linked with dextran aldehyde. The combination of oligopeptide-terminated pBAE polymers and biodegradable hydrogels shows improved transfection efficiency in vivo even when compared with the most potent commercially available transfection reagents. These results highlight the advantage of using composite materials for successful delivery of these highly promising small molecules to combat cancer.
在所有备受炒作和昂贵的癌症药物中，有前途的 siRNA 小分子药物的益处有限。缺乏有效的输送载体，无法在局部释放药物、保护药物免受降解，并确保高转染效率，限制了其充分发挥潜力。本工作提出了一种新的平台，用于在乳腺癌小鼠模型中进行局部和持续的 siRNA 传递，具有高转染效率。siRNA 的保护和高转染效率是通过将其包裹在寡肽末端的聚（β-氨基酯）（pBAE）纳米粒子中实现的。通过将 siRNA 包封在基于聚酰胺胺（PAMAM）树状大分子交联葡聚糖醛的水凝胶支架中，纳米粒子的增强稳定性实现了 siRNA 的持续传递。寡肽末端的 pBAE 聚合物和可生物降解水凝胶的组合，即使与最有效的市售转染试剂相比，也显示出了更好的体内转染效率。这些结果突出了使用复合材料成功传递这些极具前途的小分子以对抗癌症的优势。
