Idiopathic pulmonary fibrosis (IPF) is a chronic disease, causing irreversible lung scarring and respiratory failure. CD206+ M2 macrophages play a key role in its progression. In this study, we utilize the pro-inflammatory properties of plant viruses to develop a mannose-modified tobacco mosaic virus nanoparticle (TMV-OEG8-Man), which targets and reprograms profibrotic macrophages to inhibit IPF. TMV-OEG8-Man alters the CD206+ M2 macrophage phenotype in vitro, suppressing profibrotic genes (Mrc1, Spp1, Ccr2) and signaling pathways (MAPK, TGF-beta, PI3K-Akt, mTOR, Wnt), thereby reducing the transition of fibroblasts to myofibroblasts. When administered via aerosol, TMV-OEG8-Man achieves prolonged lung retention with minimal systemic exposure. In mice with bleomycin-induced pulmonary fibrosis, a single dose during fibroproliferation attenuated fibrosis progression, increasing survival rate from 50% to 100%, and preserving lung architecture. This study establishes plant viral nanoparticles as a macrophage reprogramming strategy with therapeutic potential for organ fibrosis.
Jiaodan Jin, Ren Xu, H. Fu et al.· Journal of materials chemist...· 0 citations
The formation of Pseudomonas aeruginosa (P. aeruginosa) biofilm significantly enhances bacterial resistance to antimicrobial agents and escape from the host immune system, making the treatment of related infections considerably more challenging. As a potential approach for anti-biofilm strategies, the inhibition of lectins often relies on multivalent interactions to enhance binding affinity between the inhibitor and its target. In this study, targeting the P. aeruginosa lectin LecA, we constructed a polyethylene glycol-based multivalent galactoside, termed 4-Arm-PEG-Gal, by modifying the termini of 4-Arm-PEG with galactosides specific to LecA. The results indicate that 4-Arm-PEG-Gal significantly disrupts mature biofilm and is specifically recognized by the lectin LecA. Compared to the use of antibiotics alone, the combination of 4-Arm-PEG-Gal and TOB reduces antibiotic usage by 75% and additionally eradicates 73% of the bacteria within the biofilm. Furthermore, in a model of chronic lung infection, the combination of 4-Arm-PEG-Gal and TOB cleared all bacteria from the lungs, significantly reduced the secretion of TNF-α and IL-6 in the lungs, and effectively ameliorated lung damage caused by bacterial infection.
Chen-Xiao Wan, Xiaoyan Ju, Mei-Yun Ma et al.· Journal of materials chemist...· 0 citations
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