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Amino/Amido Conjugates Form to Nanoscale Cobalt Physiometacomposite (PMC) Materials Functionally Delivering Nucleic Acid Therapeutic to Nucleus Enhancing Anticancer Activity via Ras-Targeted Protein Interference
ACS Applied Bio Materials ( IF 4.6 ) Pub Date : 2020-01-07 , DOI: 10.1021/acsabm.9b00798
Robert K DeLong 1 , John Dean 2 , Garry Glaspell 3 , Majid Jaberi-Douraki 4 , Kartik Ghosh 5 , Daniel Davis 6 , Nancy Monteiro-Riviere 1 , Parwathy Chandran 1 , Tuyen Nguyen 1 , Santosh Aryal 1 , C Russell Middaugh 7 , Seok Chan Park 1 , Seong-O Choi 1 , Meghana Ramani 1
Affiliation  

Aberrant splicing and protein interaction of Ras binding domain (RBD) are associated with melanoma drug resistance. Here, cobalt or nickel doped zinc oxide (ZnO) physiometacomposite (PMC) materials bind to RNA and peptide shown by Ninhydrin staining, UV–vis, Fourier transform infrared, and circular dichroism spectroscopy. PMCs deliver splice switching oligomer (SSO) into melanoma cells or 3-D tumor spheroids shown by flow cytometry, fluorescence microscopy, and bioluminescence. Stability in serum, liver, or tumor homogenate up to 48 h and B16F10 melanoma inhibition ≥98–99% is shown. These data suggest preclinical potential of PMC for delivery of SSO, RBD, or other nucleic acid therapeutic and anticancer peptides.

中文翻译:

氨基/氨基共轭物形成纳米级钴物理复合材料 (PMC) 材料,通过 Ras 靶向蛋白干扰向细胞核提供核酸治疗剂增强抗癌活性

Ras 结合域 (RBD) 的异常剪接和蛋白质相互作用与黑色素瘤耐药性有关。在这里,钴或镍掺杂的氧化锌 (ZnO) 生理元复合材料 (PMC) 材料与 RNA 和肽结合,通过茚三酮染色、UV-vis、傅里叶变换红外和圆二色光谱显示。PMC 将剪接转换寡聚体 (SSO) 传递到黑色素瘤细胞或流式细胞术、荧光显微镜和生物发光显示的 3-D 肿瘤球体中。血清、肝脏或肿瘤匀浆的稳定性长达 48 小时,显示 B16F10 黑色素瘤抑制≥98-99%。这些数据表明 PMC 用于递送 SSO、RBD 或其他核酸治疗和抗癌肽的临床前潜力。
更新日期:2020-01-07
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