Multivalent polymers displaying M2 macrophage-targeting peptides improve target binding avidity and serum stability.

Tumor-associated macrophages (TAMs) display a spectrum of phenotypes ranging from pro-tumoral/anti-inflammatory "M2-like" to anti-tumoral/pro-inflammatory "M1-like" subtypes and, consequently, high intratumoral M2-to-M1 ratios are typically indicative of poor disease prognosis. Cancer immunotherapies that selectively modulate M2-like TAMs, enabling reversal of the M2-to-M1 ratio, represent a promising anti-cancer intervention but are difficult to implement due to the lack of effective targeting systems. In this study, we report the development of high avidity, M2 macrophage-selective targeted drug delivery platforms based on M2 macrophage-targeting peptides (M2pep) grafted onto poly(N-(2-hydroxypropyl) methacrylamide). Furthermore, these M2pep-grafted polymers also exhibit improved serum stability along with M2 macrophage-selective toxicity.