Squalenoylation: A Novel Technology for Anticancer and Antibiotic Drugs with Enhanced Activity

Abstract

This chapter describes the ‘squalenoylation’ technology, a platform for the discovery of new nanomedicines. The design of nanomedicines is generally based on the physical encapsulation, adsorption, or entrapment of a drug in a nanocarrier. This generally results in poor drug loading, and often an uncontrolled fast release of the drug (known as burst release). To overcome those limitations, the squalenoylation concept is based on the chemical (rather than physical) loading of drugs in nanomedicines. The idea is to link a biologically active compound (anticancer, antibiotic, antiviral, MRI imaging agent, etc.) to squalene, a natural and biocompatible lipid. Due to the unique, dynamically folded molecular conformation of squalene, the resulting squalene–drug bioconjugates self-assemble spontaneously in water to form nanoparticles. The resulting nanoassemblies have been shown to have enhanced pharmacological activity, and with reduced toxicity, thus paving the way to a new concept in the field of drug delivery.