Tailoring the surface charges of iron-crosslinked dextran nanogels towards improved tumor-associated macrophage targeting

Tumor-associated macrophages (TAMs) have emerged as therapeutic interests in cancer nanomedicine because TAMs play a pivotal role in the immune microenvironment of solid tumors. Dextran and its derived nanocarriers are among the most promising nanomaterials for TAM targeting due to their intrinsic affinities towards macrophages. Various dextran-based nanomaterials have been developed to image TAMs. However, the effects of physiochemical properties especially for surface charges of dextran nanomaterials on TAM-targeting efficacy were ambiguous in literature. To figure out the surface charge effects on TAM targeting, here we developed a facile non-covalent self-assembly strategy to construct oppositely charged dextran nanogels (NGs) utilizing the coordination interaction of ferric ions, chlorine e6 (Ce6) dye and three dextran derivatives, diethylaminoethyl-, sulfate sodium- and carboxymethyl-dextran. The acquired dextran NGs exhibit different charges but similar hydrodynamic size, Ce6 loading and mechanical stiffness, which enables a side-by-side comparison of the effects of NG surface charges on TAM targeting monitored by the Ce6 fluorescence imaging. Compared with negative NGs, the positive NG clearly displays a superior TAM targeting in murine breast cancer model. This study identifies that positively charged dextran NG could be a promising approach to better engineer nanomedicine towards an improved TAM targeting.