Title : M2 macrophage-mediated targeted delivery of herbal medicines in rheumatoid arthritis
Abstract:
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and progressive joint damage; current first-line drugs provide incomplete control and dose-limiting adverse effects. Potent natural products from Traditional Chinese Medicine (TCM), exemplified by Saussurea involucrata (SI, “snow lotus”) extract and the monomer triptolide (TP) from Triptergium wilfordii (“thunder god vine”), exert strong anti-inflammatory and immunomodulatory actions, yet their clinical use is constrained by low bioavailability and systemic toxicity. Building on advances in macrophage-based drug delivery and the inflamed-tissue homing of M2-polarized macrophages, we engineered M2 cells as live carriers to enhance targeted delivery and mitigate toxicity in RA. Lipid nanoparticles (LNPs) encapsulating SI extract or TP were optimized via uniform design experiments and characterized by transmission electron microscopy and dynamic light scattering, revealing spherical morphology, narrow size distribution, and colloidal stability. THP-1-derived macrophages were polarized to the M2 phenotype, with ELISA confirming an anti-inflammatory cytokine profile consistent with successful induction. Drug-loaded, fluorescent LNPs were co-incubated with M2 cells; confocal microscopy verified robust intracellular uptake, confirming efficient cargo loading. Pharmacological evaluation in inflammatory models demonstrated that M2-delivered SI- or TP-LNPs more potently suppressed pro-inflammatory mediators and better-preserved cell viability than compared with free drugs and non-loaded controls, with notably reduced cytotoxicity. These results validate M2 macrophages as live, inflammation-homing carriers for precise delivery of SI and TP in RA. By concentrating payloads within inflamed synovium, this approach enhances efficacy while reducing off-target toxicity, thereby elevating the therapeutic index of botanical extracts and monomers. The modular platform supports safer translation of SI, TP and other potent herbal medicines, offering a broadly applicable live-cell strategy for targeted therapy in RA and other inflammatory diseases.
