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Nucleic acid aptamers are single-stranded DNA or RNA molecules identified to recognize with high affinity specific targets including proteins, small molecules, ions, whole cells and even entire organisms, such as viruses or bacteria. They can be identified from combinatorial libraries of DNA or RNA oligonucleotides by SELEX technology, an in vitro iterative selection procedure consisting of binding (capture), partitioning and amplification steps. Remarkably, many of the aptamers selected against biologically relevant protein targets are G-rich sequences that can fold into stable G-quadruplex (G4) structures. Aiming at disseminating novel inspiring ideas within the scientific community in the field of G4-structures, the emphasis of this review is placed on: 1) recent advancements in SELEX technology for the efficient and rapid identification of new candidate aptamers (introduction of microfluidic systems and next generation sequencing); 2) recurrence of G4 structures in aptamers selected by SELEX against biologically relevant protein targets; 3) discovery of several G4-forming motifs in important regulatory regions of the human or viral genome bound by endogenous proteins, which per se can result into potential aptamers; 4) an updated overview of G4-based aptamers with therapeutic potential and 5) a discussion on the most attractive G4-based aptamers for diagnostic applications. This article is part of a Special Issue entitled "G-quadruplex" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio.

Ruthenium complexes are attracting increasing attention as second‐generation metal‐based anticancer agents, with NAMI‐A and KP1019 as the major representatives of this class having undergone clinical trials. Our recent interest has been focused on the synthesis and characterization of new amphiphilic derivatives of nucleosides (nucleolipids). These compounds have been selected as core scaffolds linked to RuIII complexes and capable of self‐assembly into stable nanostructures in aq. solutions so to transport the metal ions efficiently into the cell. Through the use of ribo‐ and deoxyribonucleosides as starting building blocks, a mini‐library of nucleolipidic RuIII complexes decorated with diverse hydrophilic and lipophilic chains and incorporating the NAMI‐A analogue AziRu has been prepared. When co‐aggregated with biocompatible lipids, these RuIII‐containing nucleolipids proved to be stable for months under physiological conditions. Detailed microstructural characterization, carried out by a combined approach including different physico‐chemical techniques, allowed their stability, size and shape to be determined. Tested on a panel of human and non‐human cells, all of the studied RuIII complexes showed potent in vitro anticancer activity, significantly higher than that of NAMI‐A‐like analogues, and minimal toxicity. Here we summarize the design and synthetic procedures developed to prepare these new Ru‐containing candidate drugs, discussing the beneficial effects achievable through exploiting nucleolipid appendages in the delivery of metal‐based drugs.

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