Chemotherapeutic-caused liver toxicity hinders nanomedicine development.

Few nanomedicines are approved for clinical cancer treatment as only about 0.7% (median) of nanoparticles enter solid tumors. Nanomedicine as the second medication is usually used in cancer treatment after chemotherapy, immunotherapy surgery, or radiotherapy treatment. However, it is currently unpredictable whether the priority treatment enhances or reduces the therapeutic effect of nanomedicine. Here, by considering prior chemotherapy (5-FU or cisplatin treatment), immunotherapy (IL-2, IL-6, or IL-21-treatment), or phosphate-buffered saline (PBS treatment), we compared the biodistribution of AuNPs in the liver, spleen, kidney, and tumor. We found that the accumulation of AuNPs in the liver and spleen increased in cisplatin pretreatment compared to the PBS treatment, while there was no significant effect on the accumulation of AuNPs in the tumor due to cisplatin-induced significant liver damage while other treatments did not change the biodistribution of AuNPs in the liver, spleen, kidney, and tumor. These results indicated that cisplatin pretreatment is not suitable for subsequent nanomedical cancer therapy. Our work opens a new insight to design low-toxicity chemotherapy to be applied before nanomedicine.