Resiquimod Improves the Tumor Accumulation and Antitumor Activity of SN38 Prodrug-Loaded Liposomes.

The effectiveness of liposome-based antitumor drugs is significantly limited by the poor tumor accumulation of liposomes. Herein, we report that resiquimod (R848) can selectively increase tumor accumulation of 7-Ethyl-10-hydroxycamptothecin (SN38)-loaded liposomes (SN38-LIPs) without significantly altering their pharmacokinetics. R848 enhanced the tumor distribution of SN38-LIPs and free SN38 by approximately 5-fold and 10-fold, respectively. This further resulted in greatly improved in vivo antitumor activity compared with those treated with R848 or SN38-LIPs alone (tumor inhibition rate: ∼95% versus ∼50%). The increased antitumor activity was associated with increased serum TNF-α and enhanced macrophage infiltration in the tumor. These results suggested that R848 held great potential to enhance the clinical antitumor effect of nanomedicine by increasing its tumor accumulation.