Adenosine and lipids: A forced marriage or a love match?

Adenosine is a fascinating compound, crucial in many biochemical processes: this ubiquitous nucleoside serves as an essential building block of RNA, is also a component of ATP and regulates numerous pathophysiological mechanisms via binding to four extracellular receptors. Due to its hydrophilic nature, it belongs to a different world than lipids, and has no affinity for them. Since the 1970's, however, new discoveries have emerged and prompted the scientific community to associate adenosine with the lipid family, especially via liposomal preparations and bioconjugation. This seems to be an arranged marriage, but could it turn into a true love match? This review considered all types of unions established between adenosine and lipids. Even though exciting supramolecular structures were observed with adenosine-lipid conjugates, as well as with liposomal preparations which resulted in promising pre-clinical results, the translation of these technologies to the clinic is still limited.