Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, which can lead to disability of joint system, associated with inflammation, swelling, and pain. [1][2][3] Recent studies suggest that activated inflammatory immune cells including T cells, DCs and macrophages that infiltrate into the joint synovium are responsible for the destruction of joint and cartilage. [4,5] Current agents (e.g., glucocorticoids and nonsteroidal anti-inflammatory agents) have been widely used in clinical applications for RA treatment. [6,7] However, the response to these therapies is very low, depending on the treatment history, especially the course of disease. In addition, strong side effects like teratogenicity, hepatotoxicity, and a high risk of infection limit the use of these agents with a high-frequent dose. [8,9] Therefore, new strategy that targets the affected tissues to enhance the efficacy of RA treatment is urgently awaited. Recently, cellular delivery systems have become a promising platform for therapeutics delivery. [10][11][12][13][14] Compared with traditional carriers, cell is an inherent component of the body with excellent biocompatibility. At the same time, different types of cells have their unique biological functions, such as chemotaxis, homing properties, immune regulation, and therapeutic effects, etc., which can be utilized to facilitate drug delivery. [15][16][17] We have previously found that platelet-derived extracellular vesicles (PEVs) which are naturally occurring nanoparticles released by platelets, can selectively target different sites of various inflammation, which is a kind of universal tool for inflammation diagnosis and treatment. [18,19] Berberine (BBR) is an alkaloid widely studied for the treatment of RA due to their anti-inflammation effect. [20,21] In preclinical studies, BBR has been proven by inhibiting inflammatory proliferation of macrophages and suppressing dendritic cells activation to inhibit inflammation of synovial joints, and by participating in a variety of inflammatory signaling cascades and apoptosis-mediated pathway to ameliorate RA. [22] Here, by loading BBR into PEVs, we showed that berberine-PEVs (BBR-PEVs) could inhibit inflammation by regulating the phenotype of macrophages and dendritic cells. In RA mouse model, high accumulation of BBR-PEVs in affected joints was observed following intravenously administration. Moreover, we found that the mobility of arthritis mice has significantly improved after BBR-PEVs treatment, and the infiltration of inflammatory cells at the arthritis site significantly reduced compared to the free drug treatment group at the same dose. In short, treatment based on our strategy can effectively enhance the efficacy of RA treatment with limited side effects (Figure 1a).

Platelet extracellular vesicles are engineered to deliver dexamethasone in acute pneumonia. This drug delivery system considerably reduces the anxiety-like behavior and calms down cytokine storm compared to the mice treated with free drug.

Optogenetic therapy has emerged as a promising technique for the treatment of ocular diseases; however, most optogenetic tools rely on external blue light to activate the photoswitch, whose relatively strong phototoxicity may induce retinal damage. Herein, we present the demonstration of camouflage nanoparticle-based vectors for in situ bioluminescence-driven optogenetic therapy of retinoblastoma. In biomimetic vectors, the photoreceptor CRY2 and its interacting partner CIB1 plasmid are camouflaged with folic acid ligands and luciferase NanoLuc-modified macrophage membranes. To conduct proof-of-concept research, this study employs a mouse model of retinoblastoma. In comparison to external blue light irradiation, the developed system enables an in situ bioluminescence-activated apoptotic pathway to inhibit tumor growth with greater therapeutic efficacy, resulting in a significant reduction in ocular tumor size. Furthermore, unlike external blue light irradiation, which causes retinal damage and corneal neovascularization, the camouflage nanoparticle-based optogenetic system maintains retinal structural integrity while avoiding corneal neovascularization.

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Biomedical imaging technology, beneficial for us to peer deeply within living subjects and visually explore the delivery and distribution of agents in livings, is producing tremendous opportunities for early diagnosis...

The current vehicles used to deliver antisense oligonucleotides (ASOs) cannot distinguish between bacterial and mammalian cells, greatly hindering the preclinical or clinical treatment of bacterial infections, especially those caused by antibiotic-resistant bacteria. Herein, we leverage bacteria-specific ATP-binding cassette (ABC) transporters to selectively internalize ASOs by hitchhiking them on the unique carbon source of bacterial cells. Compared with their cell-penetrating peptide counterparts, which are non-specifically engulfed by both mammalian and bacterial cells and which display a low uptake rate (i.e. 14.7%), the presented therapeutics consisting of glucose polymer and antisense peptide nucleic acid-modified nanoparticles are selectively internalized into the human-derived multidrug-resistant Escherichia coli and methicillin-resistant Staphylococcus aureus, and they display a much higher uptake rate (i.e. 51.6%). We demonstrate that the developed strategy allows specific and efficient killing of nearly 100% of the antibiotic-resistant bacteria. We also show its significant curative efficacy against bacterial keratitis and endophthalmitis in mice. This strategy will expand the focus of antisense technology to include bacterial cells other than mammalian cells.

No abstract

Current vehicles used to deliver antisense oligonucleotides (ASOs) cannot distinguish between bacterial and mammalian cells, greatly hindering the preclinical or clinical treatment of bacterial infections, especially those caused by antibiotic‐resistant bacteria. Herein, bacteria‐specific ATP‐binding cassette (ABC) sugar transporters are leveraged to selectively internalize ASOs by hitchhiking them on α (1–4)‐glucosidically linked glucose polymers. Compared with their cell‐penetrating peptide counterparts, which are non‐specifically engulfed by mammalian and bacterial cells, the presented therapeutics consisting of glucose polymer and antisense peptide nucleic‐acid‐modified nanoparticles are selectively internalized into the human‐derived multidrug‐resistant Escherichia coli and methicillin‐resistant Staphylococcus aureus, and they display a much higher uptake rate (i.e., 51.6%). The developed strategy allows specific and efficient killing of nearly 100% of the antibiotic‐resistant bacteria. Its significant curative efficacy against bacterial keratitis and endophthalmitis is also shown. This strategy will expand the focus of antisense technology to include bacterial cells other than mammalian cells.