Chitosan Particles Complexed with CA5-HIF-1α Plasmids Increase Angiogenesis and Improve Wound Healing.
Chitosan Particles Complexed with CA5-HIF-1α Plasmids Increase Angiogenesis and Improve Wound Healing.
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与CA5-HIF-1α质粒复合的壳聚糖颗粒会增加血管生成并改善伤口愈合。
DOI：
10.3390/ijms241814095
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发表时间：
2023-09-14
影响因子：
5.6
通讯作者：
Harmon JW
中科院分区：
文献类型：
--
作者：
Born LJ;Bengali S;Hsu ATW;Abadchi SN;Chang KH;Lay F;Matsangos A;Johnson C;Jay SM;Harmon JW
由于局部治疗的优点和容易性，涉及向皮肤递送基因的伤口疗法具有显著的潜力。然而，选择合适的载体，使成功的基因表达，同时也确保治疗的直接材料成分有利于愈合本身是至关重要的。在这项研究中，我们利用聚合物壳聚糖的颗粒制剂（壳聚糖颗粒，CP）作为非病毒载体，用于递送编码人CA 5-HIF-1α（HIF-1 α的一种抗降解形式）的质粒，以促进伤口愈合。我们还比较了我们的治疗（HIF/CP）的血管生成潜力，仅含质粒骨架（bb/CP）和壳聚糖颗粒载体单独（CP）的壳聚糖颗粒。我们的研究结果表明，壳聚糖颗粒发挥血管生成作用，增强了与人CA 5-HIF-1α编码的质粒。此外，HIF/CP促进糖尿病db/db小鼠中的伤口愈合（p < 0.01），并且发现愈合的组织与bb/CP（p < 0.01）、CP（p < 0.05）和无治疗组（p < 0.01）相比含有显著增加的血管数量。因此，本研究代表了一种将基因递送至皮肤的方法，该方法利用固有的促伤口愈合聚合物作为质粒DNA的载体，该质粒DNA具有广泛的应用，用于表达其他治疗基因。
Wound therapies involving gene delivery to the skin have significant potential due to the advantage and ease of local treatment. However, choosing the appropriate vector to enable successful gene expression while also ensuring that the treatment’s immediate material components are conducive to healing itself is critical. In this study, we utilized a particulate formulation of the polymer chitosan (chitosan particles, CPs) as a non-viral vector for the delivery of a plasmid encoding human CA5-HIF-1α, a degradation resistant form of HIF-1α, to enhance wound healing. We also compared the angiogenic potential of our treatment (HIF/CPs) to that of chitosan particles containing only the plasmid backbone (bb/CPs) and the chitosan particle vector alone (CPs). Our results indicate that chitosan particles exert angiogenic effects that are enhanced with the human CA5-HIF-1α-encoded plasmid. Moreover, HIF/CPs enhanced wound healing in diabetic db/db mice (p < 0.01), and healed tissue was found to contain a significantly increased number of blood vessels compared to bb/CPs (p < 0.01), CPs (p < 0.05) and no-treatment groups (p < 0.01). Thus, this study represents a method of gene delivery to the skin that utilizes an inherently pro-wound-healing polymer as a vector for plasmid DNA that has broad application for the expression of other therapeutic genes.
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