Macrophage-Targeted Hydroxychloroquine Nanotherapeutics for Rheumatoid Arthritis Therapy

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease with unclear pathogenesis. Hydroxychloroquine (HCQ), despite its moderate anti-RA efficacy, is among the few clinical drugs used for RA therapy. Macrophages reportedly play a vital role in RA. Here, we designed and explored macrophage-targeted HCQ nanotherapeutics based on mannose-functionalized polymersomes (MP-HCQ) for RA therapy. Notably, MP-HCQ exhibited favorable properties of less than 50 nm size, glutathione-accelerated HCQ release, and M1 phenotype macrophage (M1M) targetability, leading to repolarization of macrophages to anti-inflammatory M2 phenotype (M2M), reduced secretion of pro-inflammatory cytokines (IL-6), and upregulation of anti-inflammatory cytokines (IL-10). The therapeutic studies in the zymosan-induced RA (ZIA) mouse model showed marked accumulation of MP-HCQ in the inflammation sites, ameliorated symptoms of RA joints, significantly reduced IL-6, TNF-α, and IL-1β, and increased IL-10 and TGF-β compared with free HCQ. The analyses of RA joints disclosed greatly amplified M2M and declined mature DCs, CD4+ T cells, and CD8+ T cells. In accordance, MP-HCQ significantly reduced the damage of RA joints, cartilages, and bones compared to free HCQ and non-targeted controls. Macrophage-targeted HCQ nanotherapeutics therefore appears as a highly potent treatment for RA.

Comparison of immune cells and diagnostic markers between spondyloarthritis and rheumatoid arthritis by bioinformatics analysis

“…In addition, inducing anti-inflammatory M2 macrophages, inhibiting the production of inflammatory factors and alleviating synovitis of RA are also the focus of current research. This is consistent with our experimental results [ 20 ]. Enrichment analysis also showed that cellular immune processes such as B cells differentiation, T cells proliferation, cell adhesion, cell chemotaxis and endocytosis were involved in the pathogenesis of RA.…”

Immune Effects of Macrophages in Rheumatoid Arthritis: A Bibliometric Analysis From 2000 to 2021

“…Early intervention, such as TNF blockers, can increase the rate of clinical response and the likehood of clinical symptom improvement ( 35 , 36 ). Additionally, biologics targeting on IL-1, IL-6, IL-10, IL-17 and GM-CSF are also favored by researchers, and relevant clinical trials are underway ( 37 , 38 ).…”

Application of nanotechnology in the diagnosis and treatment of acute pancreatitis

“…46,47 Meanwhile, the advantage of nanomaterial targeting is that it can target specic target cells, such as tumor cells and macrophages, with effective affinity for therapeutic purposes. 48,49 NPs have been widely reported in the diagnosis and treatment of AP. The purpose of this review is to discuss the clinical implications of the different nanoplatforms that have been published in recent years for the diagnosis and therapy of AP.…”