Drug-free biomedical polymers to control the recruitment of immune and circulating cancer cells into inflamed tissues

Vascular inflammation represents a cascade of events, including the expression of endothelial cell adhesion molecules (CAMs, e.g., ICAM-1, VCAM-1, P-selectin, E-selectin) that are involved in recruitment of leukocytes, a crucial step in physiological processes such as acute inflammation, immune response, wound repair, and hemostasis. However, excessive recruitment of leukocytes can propagate the inflammatory process and, in many cases, may aggravate tissue injury. Moreover, circulating tumor cells utilize endothelial CAMs to promote their own extravasation and the establishment of metastatic niche, which decrease the survival rate. Cell-surface receptors, including the CD44 adhesion molecule, play a major role in tethering cells to extracellular ligands, are now recognized to have broader functions in mediating cancer cell migration and metastasis. Endothelial- and cell-surface CAMs have been utilized over the years for targeting of diagnostic and therapeutic nanocarriers to pathologically activated vascular endothelium and diseased tissues.

Recent reports are corroborating the notion that nanocarriers do not necessarily need to include a drug payload but can exert biological effects through specific binding/blocking of important target molecules at the site of action. In this talk, I will provide in vivo evidence to show that pre-treatment of mice with “drug-free” copolymers, that binds CAMs with high affinity and specificity, can attenuate excessive inflammation, where infiltrating immune cells can damage the tissues and organs (e.g., heart and liver), and further inhibit the colonization of circulating cancer cells in tumor-free secondary sites. Since no low molecular weight drug is needed, the therapies have the potential advantage of avoiding side effects and reduce resistance. The polymers become effective without entering cells, and their simplicity, as compared with other polymeric systems which have to enter the cells, offers great promise for the control of inflammation and the metastatic spread of cancer.