For inflammatory bowel disease (IBD) therapy, systemic exposure of anti-TNF-α antibodies brought by current clinical injection always causes serious adverse effects. Colon-targeted delivery of anti-TNF-α antibodies through the oral route is of great importance but remains a formidable challenge. Here, we reported a biomimetic nanocomposite made of a ginger-derived exosome and an inorganic framework for this purpose. A large mesoporous silicon nanoparticle (LMSN) was uniquely customized for the antibody (infliximab, INF) to load it at high levels up to 61.3 wt% and prevent its aggregation. Exosome-like nanovesicles were isolated from ginger (GE) with a high-level production (17.5 mg kg⁻¹). Then, ultrasound was used to coat GE onto the LMSN to obtain the biomimetic nanocomposite LMSN@GE. As expected, LMSN@GE showed advantages in the oral delivery of INF: stability in the gastrointestinal tract, colon-targeted delivery and high intestinal epithelium permeability. Amazingly, GE also presented an anti-inflammatory effect by blocking the NLRP3 inflammasome in addition to its delivery value. As a result, INF/LMSN@GE showed a significantly higher efficacy in colitis mice compared to the intravenously administered INF. This work provides new insights into colon-targeted delivery of anti-TNF-α antibodies via the oral route. Moreover, it puts forward a novel strategy for drug delivery using one therapeutic agent (herb-derived exosomes).

中文翻译：

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由生姜衍生的外泌体和无机框架制成的仿生纳米复合材料，用于高性能递送口服抗体

对于炎症性肠病（IBD）治疗，目前临床注射所带来的抗TNF-α抗体全身暴露总是会导致严重的不良反应。通过口服途径靶向结肠递送抗 TNF-α 抗体非常重要，但仍然是一项艰巨的挑战。在这里，我们报告了一种由生姜衍生的外泌体和用于此目的的无机框架制成的仿生纳米复合材料。为抗体（英夫利昔单抗，INF）专门定制了一个大的介孔硅纳米颗粒 (LMSN)，以将其负载到高达 61.3 wt% 的高水平并防止其聚集。从姜 (GE) 中分离出类外泌体的纳米囊泡，产量高（17.5 mg kg ^-1）。然后，使用超声波将GE涂覆在LMSN上以获得仿生纳米复合材料LMSN@GE。正如预期的那样，LMSN@GE 在 INF 的口服递送方面显示出优势：胃肠道稳定性、结肠靶向递送和高肠上皮渗透性。令人惊讶的是，除了其传递价值外，GE 还通过阻断 NLRP3 炎性体来呈现抗炎作用。因此，与静脉注射 INF 相比，INF/LMSN@GE 在结肠炎小鼠中显示出显着更高的疗效。这项工作为通过口服途径靶向结肠递送抗 TNF-α 抗体提供了新的见解。此外，它提出了一种使用一种治疗剂（草药衍生的外泌体）进行药物递送的新策略。