小干扰RNA
内吞作用
基因沉默
细胞生物学
内体
材料科学
纳米囊
癌症研究
纳米技术
细胞
生物
转染
细胞培养
细胞内
纳米颗粒
生物化学
遗传学
基因
作者
Byungji Kim,Si Sun,Judith A. Varner,Stephen B. Howell,Erkki Ruoslahti,Michael J. Sailor
标识
DOI:10.1002/adma.201902952
摘要
Abstract Despite the promise of ribonucleic acid interference therapeutics, the delivery of oligonucleotides selectively to diseased tissues in the body, and specifically to the cellular location in the tissues needed to provide optimal therapeutic outcome, remains a significant challenge. Here, key material properties and biological mechanisms for delivery of short interfering RNAs (siRNAs) to effectively silence target‐specific cells in vivo are identified. Using porous silicon nanoparticles as the siRNA host, tumor‐targeting peptides for selective tissue homing, and fusogenic lipid coatings to induce fusion with the plasma membrane, it is shown that the uptake mechanism can be engineered to be independent of common receptor‐mediated endocytosis pathways. Two examples of the potential broad clinical applicability of this concept in a mouse xenograft model of ovarian cancer peritoneal carcinomatosis are provided: silencing the Rev3l subunit of polymerase Pol ζ to impair DNA repair in combination with cisplatin; and reprogramming tumor‐associated macrophages into a proinflammatory state.
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