title: Thioctic acid derivatives as building blocks to incorporate DNA oligonucleotides onto gold nanoparticles.
abstract: Oligonucleotide gold nanoparticle conjugates are being used as diagnostic tools and gene silencing experiments. Thiol-chemistry is mostly used to functionalize gold nanoparticles with oligonucleotides and to incorporate DNA or RNA molecules onto gold surfaces. However, the stability of such nucleic acid-gold nanoparticle conjugates in certain conditions may be a limitation due to premature break of the thiol-gold bonds followed by aggregation processes. Here, we describe a straightforward synthesis of oligonucleotides carrying thioctic acid moiety based on the use of several thioctic acid-L-threoninol derivatives containing different spacers, including triglycine, short polyethyleneglycol, or aliphatic spacers. The novel thioctic-oligonucleotides were used for the functionalization of gold nanoparticles and the surface coverage and stability of the resulting thioctic-oligonucleotide gold nanoparticles were assessed. In all cases gold nanoparticles functionalized with thioctic-oligonucleotides had higher loadings and higher stability in the presence of thiols than gold nanoparticles prepared with commercially available thiol-oligonucleotides. Furthermore, the thioctic derivative carrying the triglycine linker is sensitive to cathepsin B present in endosomes. In this way this derivative may be interesting for the cellular delivery of therapeutic oligonucleotides as these results provides the basis for a potential endosomal escape.
authors.affiliation: Institute for Advanced Chemistry of Catalonia (IQAC), Consejo Superior de Investigaciones Científicas (CSIC), Jordi Girona 18-26, E-08034 Barcelona, Spain. sonia.perez@iqac.csic.es.
authors.forename: Sónia
authors.initials: S
authors.lastname: Pérez-Rentero
authors.affiliation: Institute for Advanced Chemistry of Catalonia (IQAC), Consejo Superior de Investigaciones Científicas (CSIC), Jordi Girona 18-26, E-08034 Barcelona, Spain. santiago.grijalvo@iqac.csic.es.
authors.forename: Santiago
authors.initials: S
authors.lastname: Grijalvo
authors.affiliation: Institute for Advanced Chemistry of Catalonia (IQAC), Consejo Superior de Investigaciones Científicas (CSIC), Jordi Girona 18-26, E-08034 Barcelona, Spain. guillemph90@gmail.com.
authors.forename: Guillem
authors.initials: G
authors.lastname: Peñuelas
authors.affiliation: Institute for Advanced Chemistry of Catalonia (IQAC), Consejo Superior de Investigaciones Científicas (CSIC), Jordi Girona 18-26, E-08034 Barcelona, Spain. carme.fabrega@iqac.csic.es.
authors.forename: Carme
authors.initials: C
authors.lastname: Fàbrega
authors.affiliation: Institute for Advanced Chemistry of Catalonia (IQAC), Consejo Superior de Investigaciones Científicas (CSIC), Jordi Girona 18-26, E-08034 Barcelona, Spain. recgma@cid.csic.es.
authors.forename: Ramon
authors.initials: R
authors.lastname: Eritja
mesh_terms: D006046:Gold / Q000737:chemistry*; D053768:Metal Nanoparticles / Q000737:chemistry*; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis* / Q000737:chemistry*; D008063:Thioctic Acid / Q000031:analogs & derivatives* / Q000737:chemistry*
chemical_list: D009838:Oligodeoxyribonucleotides; D008063:Thioctic Acid; D006046:Gold