Recognition of Dextran–Superparamagnetic Iron Oxide Nanoparticle Conjugates (Feridex) via Macrophage Scavenger Receptor Charged Domains

Dextran-coated superparamagnetic iron oxide nanoparticles (dextran–SPIO conjugates) offer the attractive possibility of enhancing MRI imaging sensitivity so that small or diffuse lesions can be detected. However, systemically injected SPIOs are rapidly removed by macrophages. We engineered embryonic cells (HEK293T) to express major macrophage scavenger receptor (SR) subtypes including SR-AI, MARCO, and endothelial receptor collectin-12. These SRs possess a positively charged collagen-like (CL) domain and they promoted SPIO uptake, while the charge neutral lipoprotein receptor SR-BI did not. In silico modeling indicated a positive net charge on the CL domain and a net negative charge on the cysteine-rich (CR) domain of MARCO and SR-AI. In vitro experiments revealed that CR domain deletion in SR-AI boosted uptake of SPIO 3-fold, while deletion of MARCO’s CR domain abolished this uptake. These data suggest that future studies might productively focus on the validation and further exploration of SR charge fields in SPIO recognition

Additional file 1: of Hypoestoxide reduces neuroinflammation and α-synuclein accumulation in a mouse model of Parkinson’s disease

Hypoestoxide reduces human α-synuclein accumulation in a mouse model of PD. Mice brain sections were inmmunostained against human α-synuclein (Syn211 antibody) or C-terminal of human α-synuclein (Syn105 antibody). a Immunofluorescence analysis of human α-synuclein in the frontal cortex of non-tg and α-syn-tg mice treated with either vehicle or hypoestoxide. (n = 5 per group; unpaired t test; *p < 0.05). Error bars represent ± SEM. b Fluorescence intensity against human α-synuclein was analyzed in frontal cortex of the brains. c Immunohistochemical analysis of C-terminal of human α-synuclein in the frontal cortex of non-tg and α-syn-tg mice. d Optical density analysis for C-terminal of α-synuclein in frontal cortex. (n = 5 per group; unpaired t test; **p < 0.01). Error bars represent ± SEM. Scale bars = 250 μm (low magnification) and 25 μm (high magnification). (TIF 13692 kb