Nanoscale Liposomes Co-Loaded with Irinotecan Hydrochloride and Thalidomide for Colorectal Cancer Synergistic Therapy

Macromol Biosci. 2024 Dec 20:e2400478. doi: 10.1002/mabi.202400478. Online ahead of print.

Abstract

Irinotecan hydrochloride (CPT-11) is one of the first-line drugs used in the clinical treatment of colorectal cancer (CRC). However, the concomitant adverse effect of delayed diarrhea has hindered its clinical use. CPT-11 combined with Thalidomide (THA) therapy is considered a palliative strategy. To optimize the synergistic treatment of CPT-11 and THA, co-loaded liposomes are constructed using cholesterol, lecithin, and 1, 2-Distearoyl-sn-glycero-3-phosphoethanolamine-Poly(ethylene glycol) (DSPE-PEG) as the "immune and gut microbiota regulator." The co-loaded liposomes, which possess good stability, are prepared by the solvent injection method. After the treatment with the co-loaded liposomes, tumor growth in CRC-bearing mice is significantly inhibited. In particular, the co-loaded liposomes demonstrate favorable diarrhea-relieving effects through the modulation of inflammatory cytokines and gut microbiota. These findings suggest that the co-loaded liposomes have great potential as a combined drug-delivery platform for CRC therapy.

Keywords: colorectal cancer synergistic therapy; gut microbiota regulate; irinotecan hydrochloride; liposomes; thalidomide.