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PNAS Plus Significance Statements

We identified (pp. E217–E226) that the chemical linkage of the anticancer drug doxorubicin onto squalene, a natural lipid precursor of the cholesterol’s biosynthesis, led to the formation of squalenoyl doxorubicin nanoassemblies of 130-nm mean diameter, with an original “loop-train” structure. This unique nanomedicine demonstrates: (i) high drug payload, (ii) decreased toxicity of the coupled anticancer compound, (iii) improved therapeutic response, (iv) use of biocompatible transporter material, and (v) ease of preparation, all criteria that are not combined in the currently available nanodrugs. Taken together, these findings demonstrate that the squalenoylated doxorubicin nanoassemblies make tumor cells more sensitive to doxorubicin and reduce the cardiac toxicity.