This study showed that conjugating the anticancer drug doxorubicin to squaline, a natural lipid precursor of cholesterol, improved its anticancer efficacy and reduced its cardiotoxicity. Doxorubicin–squalene (SQ–Dox) conjugates formed nanoassemblies that reduced pancreatic tumour growth by 95% when administered to a mouse model, compared to a 29% reduction with normal doxorubicin. Moreover, murine lung tumours that did not respond to normal doxorubicin treatment were inhibited by 90% with SQ–Dox. In addition, the nanomedicine had a fivefold higher maximum tolerated dose than the unmodified drug, and unlike doxorubicin it did not cause myocardial lesions.