Reducing anaphylaxis reactions and enhancing antiarthritic effects of folate-conjugated sinomenine-loaded human serum albumin nanoparticles in experimental inflammation and arthritis

Abstract Precision targeted delivery system based on nanomaterials is a feasible strategy to address anaphylaxis reactions of natural products. By loading sinomenine (SIN) into folate (FA) modified human serum albumin (HSA) nanomaterials, triple targeting including extravasation through leaky vasculature and subsequent Inflammatory cell-mediated sequestration (ELVIS) targeting, secreted protein acidic and rich in cysteine (SPARC) targeting and M1 macrophage targeting can be achieved, and the occurrence of anaphylaxis reactions can be reduced, so that SIN can be accurately delivered to rheumatoid arthritis (RA) joints. FA-SIN-HSA NPs exhibited potent anti-inflammatory activity and analgesic effect, and the possibility of inducing anaphylaxis reactions was extremely slight. FA-SIN-HSA NPs were also able to specifically target RA joints to prolong the circulating half-life of SIN as confirmed by highperformance liquid chromatography (HPLC) and in vivo fluorescence imaging. After collagen-II induced arthritis (CIA) mice were treated with FA-SIN-HSA NPs, the symptoms were greatly relieved, and the RA therapeutic effect was excellent. Taking this case as a reference, for anaphylaxis reactions of natural products, natural products can be loaded in nanomaterials modified with targeted modifiers to enhance the therapeutic effect and reduce anaphylaxis reactions.