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首页> 外文期刊>Acta biomaterialia >Oligonucleotide-functionalized hydrogels for sustained release of small molecule (aptamer) therapeutics
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Oligonucleotide-functionalized hydrogels for sustained release of small molecule (aptamer) therapeutics

机译：寡核苷酸官能化水凝胶，用于持续释放小分子（适体）治疗剂

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Natural and synthetic hydrogels have been widely investigated as biomaterial scaffolds to promote tissue repair and regeneration. Nevertheless, the scaffold alone is often insufficient to drive new tissue growth, instead requiring continuous delivery of therapeutics, such as proteins or other biomolecules that work in concert with structural support provided by the scaffold. However, because of the high-water content. hydrogels tend to be permeable and cause rapid release of the encapsulated drug, which could lead to serious complications from local overdose and may result in the significant waste of encapsulated therapeutic(s). To this end, we designed an oligonucleotide-functionalized hydrogel that can provide sustained and controlled delivery of therapeutics for up to 4 weeks. To prove this concept, we successfully achieved sustained release (for over 28 days) of model anti-Nogo receptor (anti-NgR) RNA aptamer from oligonucleotide-functionalized hyaluronic acid-based hydrogel by changing the complementarity between the short antisense sequences and the aptamer. Furthermore, the released aptamer successfully blocked neuro-inhibitory effects of myelin-derived inhibitors and promoted neurite outgrowth from rat dorsal root ganglia in vitro. Because antisense sequences can be designed to bind to proteins, peptides, and aptamer, our oligonucleotide-functionalized hydrogel offers a promising therapeutic delivery system to obtain controlled release (both bolus and sustained) of various therapeutics for the treatment of complex diseases and injury models, such as spinal cord injury.
机译：天然和合成水凝胶已被广泛研究为生物材料支架，以促进组织修复和再生。然而，单独的支架通常不足以推动新的组织生长，而是需要连续递送治疗剂，例如用支架提供的结构支撑作用的蛋白质或其他生物分子。但是，由于高含水量。水凝胶往往是可渗透的并且导致包封的药物的快速释放，这可能导致局部过量的严重并发症，并且可能导致封装治疗的显着浪费。为此，我们设计了寡核苷酸官能化的水凝胶，可提供持续和控制的治疗剂递送长达4周。为了证明这一概念，我们通过改变短反义序列和适体之间的互补性，成功地从寡核苷酸官能化透明质酸基水凝胶中获得了模型抗Nogo受体（抗NgR）RNA适体的持续释放（持续28天）。 。此外，释放的适体成功阻断了髓鞘衍生抑制剂的神经抑制作用，并在体外促进了大鼠背根神经节的神经突生长。由于反义序列可以设计成与蛋白质，肽和适体结合，所以我们的寡核苷酸 - 官能化的水凝胶提供了有希望的治疗递送系统，以获得各种治疗方法的控制释放（推注和持续），用于治疗复杂疾病和伤害模型，如脊髓损伤。

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