In the frame of the NANOTRUCK project (NanoSciEranet+ (2009-2012): “Multifunctional gold nanoparticles for gene therapy”), we developed a multifunctional AuNP to deliver at high efficiency small interfering RNA and tested its capability to elicit specific gene silencing in cells, Hydra and mouse.

 

Two different approaches have been used to link siRNA to the surface of the AuNPs:

a.ionic approach, where the siRNA is linked to positively charged AuNPs just by ionic                       interactions

  1. b.covalent approach, where thiolated siRNA sequences were used to allowfurther Au-S bonds between the NPs and the siRNA.

  2. Selection of the most active functionalities was assisted step by step through functional testing adopting this hierarchical strategy (cell cultures, Hydra and mouse; qRT-PCR, Western Blot, Immunolocalization, TEM)

  3. From the 18 different AuNPs prepared along this project, only one was able to induce c-myc silencing in the three biological systems used. This AuNP obtained by the covalent approach and containing RGD and siRNA is for instance, a safe, non-pathogenic, self-tracking and universally valid nanocarrier that could be exploited for therapeutic RNAi.

Relevant Publications

  1. 1.Conde J, Ambrosone A, Hernandez Y, Tian F, McCully M, Berry CC, Baptista PV, Tortiglione C, de la Fuente JM.15 years on siRNA delivery: beyond the State-of-the-Art on inorganic nanoparticles for RNAi Therapeutics.  Nano Today 2015, 10 (4) 421–450

  2. 2.Conde J, Ambrosone A, Sanz V, Hernandez Y, Marchesano V, Tian F, Child H, Berry CC, Ibarra MR, Baptista PV, Tortiglione C, de la Fuente JM (2012) Design of Multifunctional Gold Nanoparticles for In Vitro and In Vivo Gene Silencing. ACS Nano 6 (9), 8316–8324. http://pubs.acs.org/doi/abs/10.1021/nn3030223

  3. 3.Ambrosone A, Marchesano V, Tino A, Hobmayer B, Tortiglione C. Hymyc1 Downregulation Promotes Stem Cell Proliferation in Hydra vulgaris. PLoS One. 2012;7(1):e30660. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0030660

Gold NANOPARTICLES FOR GENE SILENCING

Go to: NANOMEDICINE

Collaborations

Jesus de la Fuente, Instituto de Nanociencia y Materiales de Aragón (INMA), Zaragoza, Spain