Can therapeutic potency of a cancer nanomedicine be predicted by pain-related behavioral test in subcutaneous tumor model?

Cancer nanomedicines have shown great potential in fighting against cancer. While the development of cancer nanomedicines is advancing rapidly, preclinical assessment approaches for their therapeutic potency have stagnated. In view of high prevalence of cancer pain in cancer patients, we aim to determine whether therapeutic potency of a cancer nanomedicine can be predicted by pain-related behavioral test in subcutaneous tumor model, the simplest and most widely used tumor model in oncology. Behavioral profiles reveal that subcutaneous tumor, probably irrespective of tumor type, presents with spontaneous pain (open field test) and evoked pain (von Frey test for mechanical allodynia; Hargreaves test, hot plate test, and tail flick test for thermal hyperalgesia; cold plate test and acetone drop test for thermal allodynia). Using doxorubicin (DOX)-loaded lipid nanoparticles (LNPs) (LNPs/DOX) as a representative cancer nanomedicine and ropivacaine (ROP)-loaded LNPs (LNPs/ROP) as a pain nanomedicine, it is validated that inhibiting subcutaneous tumor growth can relieve cancer pain, while delaying the growth cannot, despite a significant difference found compared with non-treatment group. Moreover, behavioral results in all the tests are consistent and von Frey test is suggested the most sensitive among them. It is strongly suggested that pain-related behavioral test can serve as a powerful tool to predict therapeutic potency of a cancer nanomedicine <i>in vivo</i> in treating subcutaneous tumor.