Tumour-associated macrophages (TAMs) are macrophages in the tumour microenvironment and play pivotal roles in cancer development and metastasis. Elimination of these cells has in the recent years emerged as a promising strategy to inhibit tumour growth and infiltration. Here we report the development of a drug delivery vehicle for targeted delivery of therapeutic agents to suppress or even eliminate TAMs. The core component of this system is a natural polysaccharide, namely BSP, isolated from the traditional Chinese medicinal herb Bletilla striata and characterised to comprise mannose and glucose (~ 2.4:1) units. We demonstrate that the mannose unit of BSP has affinity for the mannose receptor that exists on all macrophage types but is particularly highly expressed on TAMs. Alendronate sodium (AS), an established macrophage-killing agent, has successfully been conjugated to the chain of the partial oxidised BSP. Further tests including 1) cell proliferation assay on variably polarised macrophages, 2) gene expression study on major macrophage-produced cytokines, 3) molecular size screening and 4) cell targeting assay suggest that this engineered polysaccharide vehicle has desirable TAM-targeting capability and inhibits the growth of these cells. In summary, this natural polysaccharide based vehicle is an efficient drug delivery system with considerable potential to be used for the delivery of TAM-killing agents, and may open up a new avenue of enhancing the performance of tumour immunotherapy.
