Nucleolipid nanovectors as molecular carriers for potential applications in drug delivery

Abstract

Novel thymidine- or uridine-based nucleolipids, containing one hydrophilic oligo(ethylene glycol) chain and one or two oleic acid residues (called ToThy, HoThy and DoHu), have been synthesized with the aim to develop bio-compatible nanocarriers for drug delivery and/or produce pro-drugs. Microstructural characterization of their aggregates has been determined in pure water and in pseudo-physiological conditions through DLS and SANS experiments. In all cases stable vesicles, with mean hydrodynamic radii ranging between 120 nm and 250 nm have been revealed. Biological validation of the nucleolipidic nanocarriers was ensured by evaluation of their toxicological profiles, performed by administration of the nanoaggregates to a panel of different cell lines. ToThy exhibited a weak cytotoxicity and, at high concentration, some ability to interfere with cell viability and/or proliferation. In contrast, DoHu and HoThy exhibited no toxicological relevance, behaving similarly to POPC-based liposomes, widely used for systemic drug delivery. Taken together, these results show nucleolipid-based nanocarriers as finely tunable, multi-functional self-assembling materials of interest for the in vivo transport of biomolecules or drugs.

Design, Synthesis and Characterisation of Guanosine‐Based Amphiphiles

“…[19] This lead to compound 14, which was desilylated, coupled with myristic acid at the 5'-OH group, and then deprotected at the guanine moiety.…”

“…TBDPS-group removal was achieved by treatment of 5 with the Et 3 N·3HF in THF, leading to target compound 6 in 70 % overall yield from 3. G1 was then obtained in almost quantitative yields in two steps, involving first the coupling of 5'-OH-deprotected nucleoside 6 with monomethoxy(triethylene glycol) acetic acid, previously prepared in our laboratory, [19] by using DCC as the condensing agent, followed by an acidic treatment with TFA (10 %) in CH 2 Cl 2 for 2 h at RT, to achieve full nucleobase deprotection.…”

Antiproliferative effects of ruthenium-based nucleolipidic nanoaggregates in human models of breast cancer in vitro: insights into their mode of action

“…1 along with AziRu) were prepared by reacting in stoichiometric amounts the starting nucleolipids, named ToThy or DoHu57, with the Ru complex [ trans -RuCl 4 (DMSO) 2 ] − Na + following a previously described procedure25. In all cases, the desired nucleolipidic Ru(III) complexes were obtained in a pure form, as confirmed by TLC and ESI-MS analysis, and almost quantitative yields.…”

RuIII Complexes for Anticancer Therapy: The Importance of Being Nucleolipidic

“…This leads to partial hydrolysis of the complexes and eventually to formation of polyoxo species. [88][89][90][105][106][107][108][109] [101,104] Thus, in order to obtain long-lived Ru III -based antineoplastic agents, a prodrug approach, involving the decoration of the ruthenium complex with amphiphilic nanovectors, has been proposed by Paduano et al for the in vivo delivery of these compounds.…”