Wenjie Wang,Muhammad Adeel Ghafar,Lu Liuyang,Inzamam Ul Haq,Li Cui,Huizhu Yuan,Liande Wang
RNA pesticides have emerged as a promising alternative to conventional chemical pesticides due to their high specificity and minimal environmental impact. However, the instability of RNA molecules in the environment and the challenges associated with their effective delivery to target pests limit their broader application. This study addresses these challenges by developing a dual delivery system using chitosan (CS) and Metal–Organic Frameworks (MOFs) to enhance the delivery and efficacy of double-stranded RNA (dsRNA) and cycloxaprid against Diaphorina citri, a vector of citrus greening disease. The CS-MOF nanoparticles were synthesized and characterized using scanning electron microscopy (SEM) and dynamic light scattering (DLS). Insect bioassays demonstrated that the codelivery system significantly improved insecticidal activity, achieving over 80% mortality in D. citri within 2 days. The results indicate that the encapsulation of dsRNA within MOFs enhances its stability, while the controlled release properties of the nanoparticles improve the efficacy of cycloxaprid. This novel approach shows great potential in overcoming the limitations of RNA pesticides and offers a sustainable solution for pest management in agriculture. Future research should optimize the delivery system, conduct field trials, and explore its applicability to other agricultural pests.
Three-dimensional (3D) printing has been increasingly employed to produce advanced bone tissue engineering scaffolds with biomimetic structures and matched mechanical strengths, in order to induce improved bone regeneration in defects with a critical size. Given that the successful bone regeneration requires both excellent osteogenesis and vascularization, endowing scaffolds with both strong bone forming ability and favorable angiogenic potential would be highly desirable to induce improved bone regeneration with required vascularization. In this investigation, customized bone tissue engineering scaffolds with balanced osteoconductivity/osteoinductivity were produced via cryogenic 3D printing of β-tricalcium phosphate and osteogenic peptide (OP) containing water/poly(lactic- co -glycolic acid)/dichloromethane emulsion inks. The fabricated scaffolds had a hierarchically porous structure and were mechanically comparable to human cancellous bone. Angiogenic peptide (AP) containing collagen I hydrogel was then coated on scaffold surface to further provide scaffolds with angiogenic capability. A sequential release with a quick AP release and a slow but sustained OP release was obtained for the scaffolds. Both rat endothelial cells (ECs) and rat bone marrow derived mesenchymal stem cells (MSCs) showed high viability on scaffolds. Improved in vitro migration and angiogenesis of ECs were obtained for scaffolds delivered with AP while enhanced osteogenic differentiation was observed in scaffolds containing OP. The in vivo results showed that, toward scaffolds containing both AP and OP, the quick release of AP induced obvious angiogenesis in vivo , while the sustained OP release significantly improved the new bone formation. This study provides a facile method to produce dual-delivery scaffolds to achieve multiple functions.
Abnormal proliferation of aggressive fibroblast-like synoviocytes (FLS) and perpetuate synovial inflammation can inevitably accelerate the progression of rheumatoid arthritis (RA). Herein, a strategy of simultaneously promoting FLS apoptosis and inhibiting inflammation as mediated by macrophages is proposed to restore synovial homeostasis for effective RA therapy. A hyaluronic acid-based dissolvable microneedle (MN) is fabricated for transdermal delivery of dual human serum albumin (HSA)-contained biomimetic nanocomplexes to regulate RA FLS and macrophages. Upon skin insertion, dual nanocomplexes are released rapidly from the MN and accumulate in RA joint microenvironment through both passive and active targeting as mediated by HSA. Thioketal-crosslinked fluorinated polyethyleneimine 1.8 K ( TK PF) was constructed to bind the plasmid encoding pro-apoptotic gene PUMA with HSA coating layer ( TK PF/pPUMA@HSA, TPH). TPH nanocomplexes can upregulate PUMA through RA FLS transfection to trigger efficient apoptosis. Also, HSA nanocomplexes encapsulating the classic anti-inflammatory natural product celastrol (Cel@HSA, CH) can inhibit inflammation of macrophages through blocking NF-κB pathway activation. TPH/CH MN can deplete RA FLS and inhibit M1 macrophage activation, suppress synovial hyperplasia as well as reduce bone and cartilage erosion in a collagen-induced arthritis (CIA) mouse model, demonstrating a promising strategy for efficient RA treatment.
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