使用基于肽的纳米复合物靶向抗微小RNA以抑制人胰腺星状细胞的分化。
Anti-microRNA targeting using peptide-based nanocomplexes to inhibit differentiation of human pancreatic stellate cells.
作者信息
Schnittert Jonas, Kuninty Praneeth R, Bystry Tomasz F, Brock Roland, Storm Gert, Prakash Jai
机构信息
Department of Biomaterials, Science & Technology, Section: Targeted Therapeutics, MIRA Institute for Biomedical Technology & Technical Medicine, University of Twente, Enschede, The Netherlands.
Department of Biochemistry, Radboud Institute for Molecular LifeSciences, Radboud University Medical Center, Nijmegen, The Netherlands.
出版信息
Nanomedicine (Lond). 2017 Jun;12(12):1369-1384. doi: 10.2217/nnm-2017-0054. Epub 2017 May 19.
AIM
To develop novel peptide-based nanocomplexes (NCs) for delivery of anti-miRNA oligonucleotides to human-derived pancreatic stellate cells (hPSCs), precursors of cancer-associated fibroblasts.
MATERIALS & METHODS: NCs of anti-miRNA oligonucleotides and cell-penetrating peptides (different variants) were formed and characterized. The effects of anti-miR-199a delivery on hPSC differentiation and 3D heterospheroid formation were investigated.
RESULTS
Dimeric cell-penetrating peptide based NCs (NC-2) showed 130-fold higher uptake by hPSCs compared with monomer-based NCs (NC-1) and tenfold higher uptake compared with general fibroblasts and different pancreatic tumor cells. Interestingly, delivery of anti-miR-199a inhibited hPSC differentiation into cancer-associated fibroblasts and inhibited the size of 3D heterospheroids comprised of hPSCs and tumor cells.
CONCLUSION
Our NCs present a highly efficient anti-miRNA delivery system to hPSCs to inhibit their protumorigenic activity.
目的
开发新型基于肽的纳米复合物（NCs），用于将抗 miRNA 寡核苷酸递送至人源胰腺星状细胞（hPSCs），即癌症相关成纤维细胞的前体。
材料与方法
形成并表征了抗 miRNA 寡核苷酸与细胞穿透肽（不同变体）的 NCs。研究了抗 miR-199a 递送对 hPSC 分化和三维异质球体形成的影响。
结果
基于二聚体细胞穿透肽的 NCs（NC-2）被 hPSCs 的摄取量比基于单体的 NCs（NC-1）高 130 倍，比普通成纤维细胞和不同胰腺肿瘤细胞高 10 倍。有趣的是，抗 miR-199a 的递送抑制了 hPSC 向癌症相关成纤维细胞的分化，并抑制了由 hPSC 和肿瘤细胞组成的三维异质球体的大小。
结论
我们的 NCs 为 hPSCs 提供了一种高效的抗 miRNA递送系统，以抑制其促肿瘤活性。
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