Chemotherapy is one of the main treatments for cancer; however, it usually causes severe atrophy of immune organs and self-immunity damage to patients. Human lactoferrin (hLF) is a multiple biofunctional protein in regulating the immune response and thus holds great promise to alleviate chemotherapy-caused immunosuppression. However, a sufficient hLF resource and efficient delivery of hLF remain a challenge. Here, we provide a useful strategy to simultaneously solve these two problems. A silk sericin hydrogel system delivering recombinant hLF (SSH-rhLF) was fabricated to alleviate the chemotherapeutic drug-caused side effects by rhLF-carrying silk cocoons, which were cost-effectively produced by a transgenic silkworm strain as the resource. SSH-rhLF with a uniform porous microstructural morphology, a dominant β-sheet internal structure, adjustable concentration and sustainable release of the rhLF, and non-cytotoxicity properties was demonstrated. Interestingly, the sericin hydrogel showed effective protection of the rhLF from degradation in the stomach and small intestine, thus prolonging the bioactivity and bioavailability of rhLF. As a result, the oral administration of SSH-rhLF with a low rhLF dose showed significant therapeutic effects on enhancing the immune organs of cyclophosphamide (CTX)-treated mice by protecting the splenic follicles, promoting the expression of immunoregulatory factors, and recovering the intestinal flora family from CTX-induced imbalance, which were similar to those achieved by oral administration of a high dose of free hLF in the solution form. The results suggest that the strategy of producing rhLF silk cocoons via feeding transgenic silkworms overcomes well the shortage of rhLF resources, improves the bioavailability of oral rhLF, and alleviates the side effects of chemotherapeutic drugs on immune organs. The oral SSH-rhLF will be promising for applications in cancer chemotherapy and immunity enhancement of patients.

中文翻译：

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制造丝胶蛋白水凝胶系统，使用具有改善生物利用度的基因工程蚕丝递送人乳铁蛋白，以减轻化疗诱导的免疫抑制

化疗是癌症的主要治疗方法之一；但是，它通常会导致免疫器官的严重萎缩和对患者的自身免疫损伤。人乳铁蛋白 (hLF) 是一种调节免疫反应的多种生物功能蛋白，因此在缓解化疗引起的免疫抑制方面具有很大的前景。然而，充足的 hLF 资源和 hLF 的有效交付仍然是一个挑战。在这里，我们提供了一个有用的策略来同时解决这两个问题。制备了一种递送重组 hLF (SSH-rhLF) 的丝胶水凝胶系统，以减轻携带 rhLF 的丝茧的化疗药物引起的副作用，该丝茧是由转基因蚕品系作为资源生产的，具有成本效益。SSH-rhLF 具有均匀的多孔微结构形态，主要的 β-折叠内部结构，证明了 rhLF 的可调节浓度和可持续释放，以及非细胞毒性特性。有趣的是，丝胶水凝胶能有效保护 rhLF 在胃和小肠中免于降解，从而延长 rhLF 的生物活性和生物利用度。结果表明，口服低rhLF剂量的SSH-rhLF通过保护脾滤泡、促进免疫调节因子的表达和恢复肠道，对增强环磷酰胺（CTX）治疗小鼠的免疫器官表现出显着的治疗作用。来自 CTX 诱导的失衡的菌群家族，这与口服溶液形式的高剂量游离 hLF 所获得的菌群家族相似。结果表明，转基因蚕制rhLF蚕茧策略很好地克服了rhLF资源短缺的问题，提高了口服rhLF的生物利用度，减轻了化疗药物对免疫器官的副作用。口服 SSH-rhLF 在癌症化疗和患者免疫增强方面的应用前景广阔。