CIGMH, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Caparica, Portugal.
Biomaterials. 2013 Mar;34(10):2516-23. doi: 10.1016/j.biomaterials.2012.12.015. Epub 2013 Jan 11.
The potential of a single molecular nanoconjugate to intersect all RNA pathways: from gene specific downregulation to silencing the silencers, i.e. siRNA and miRNA pathways, is demonstrated. Gold-nanobeacons are capable of efficiently silencing single gene expression, exogenous siRNA and endogenous miRNAs while yielding a quantifiable fluorescence signal directly proportional to the level of silencing. The silencing potential is comparable to that of traditional siRNA but the same nanoconjugates structure is also capable of reversing the effect of an exogenous siRNA. We further demonstrate the Gold-nanobeacons' efficiency at targeting and silencing miR-21, an endogenous miRNA involved in cancer development, which could become a valid nanotheranostics approach. Again, expression of miR-21 was inhibited with concomitant increase of the Au-nanobeacons' fluorescence that can be used to assess the silencing effect. This way, a single nanostructure can be used to intersect all RNA regulatory pathways while allowing for direct assessment of effective silencing and cell localization via a quantifiable fluorescence signal, making cancer nanotheranostics possible.
单个分子纳米复合物具有干扰所有 RNA 途径的潜力:从基因特异性下调到沉默沉默子,即 siRNA 和 miRNA 途径,已得到证实。金纳米荧光探针能够有效地沉默单个基因的表达、外源性 siRNA 和内源性 miRNAs,同时产生与沉默程度成正比的可量化荧光信号。其沉默效果可与传统 siRNA 相媲美,但相同的纳米复合物结构也能够逆转外源性 siRNA 的作用。我们进一步证明了金纳米荧光探针靶向和沉默 miR-21 的效率,miR-21 是一种参与癌症发展的内源性 miRNA,它可能成为一种有效的纳米治疗方法。同样,miR-21 的表达被抑制,同时伴随着 Au-纳米荧光探针荧光的增加,可用于评估沉默效果。这样,单个纳米结构可用于干扰所有 RNA 调控途径,同时通过可量化的荧光信号直接评估有效沉默和细胞定位,使癌症纳米治疗成为可能。