Micelle nanovehicles for co-delivery of Lepidium meyenii Walp. (maca) polysaccharide and chloroquine to tumor-associated macrophages for synergistic cancer immunotherapy

Abstract

Here, we fabricated amphiphilic polysaccharide micelles for synergistic cancer immunotherapy targeting tumor-associated macrophages (TAMs). Lepidium meyenii Walp. (maca) polysaccharide (MP), a naturally derived macromolecule with a strong TAM-remodeling effect, was grafted on a hydrophobic poly(lactic-co-glycolic acid) (PLGA) segment, with a disulfide bond for redox-sensitive linkage. The amphiphilic polysaccharide derivatives could self-assemble into core (PLGA)-shell (MP)-structured micelles and encapsulate chloroquine (CQ) into the hydrophobic core. By using a 4T1-M2 macrophage co-culture model and a 4T1 tumor xenograft mouse model, we showed that the prepared micelles could co-deliver MP and CQ to the tumor sites and selectively accumulate at TAMs because of the specific properties of MP. Furthermore, the nanoparticles exerted synergistic tumor immunotherapeutic and antimetastatic effects, which might be attributable to the enhanced cell internalization of the micelles and the multiple regulatory mechanisms of MP and CQ. Thus, immunomodulatory MP may be a promising biomaterial for cancer immunotherapy.

Keywords: Amphiphilic graft copolymer; Biomacromolecule; Immunotherapy; Lepidium meyenii Walp.; Maca polysaccharide; Tumor-associated macrophages.