Monocyte-adhesive peptidyl liposomes for harnessing monocyte homing to tumor tissues

Abstract

In current drug delivery strategies, the efficiency of most carriers still largely depends on their ability to passively infiltrate target tissues. To overcome this limitation, we developed monocyte-adhesive peptidyl liposomes, termed monocyte-mediated drug carriers (MMDCs). These carriers are designed to exploit the innate chemotactic properties of monocytes, which actively home to diseased tissues. MMDCs were shown to effectively hitchhike on circulating monocytes (THP-1 cells) under physiological flow conditions. Their targeting specificity was further demonstrated in a 3D microfluidic culture system consisting of human breast cancer spheroids (MDA-MB-231) embedded in a collagen matrix, overlaid with a human endothelial cell-derived barrier. MMDCs underwent trans-endothelial migration via monocyte hitchhiking and selectively recognized collagen matrices containing MDA-MB-231 cells, but not those embedded with non-cancerous cells. In vitro assays revealed that doxorubicin encapsulated in MMDCs was released into the extracellular environment following phagocytosis of the carriers by THP-1-derived macrophages. In a xenograft mouse model, MMDCs exhibited high tumor-targeting efficiency. By harnessing the homing capability of monocytes, MMDCs significantly improved drug biodistribution at the disease site, thereby enhancing the therapeutic efficacy of the encapsulated agents.