Self-assembling natural drug hydrogels formed without structural modification and able to act as carriers are of interest for biomedical applications. A lack of knowledge about natural drug gels limits there current application. Here, we report on rhein, a herbal natural product, which is directly self-assembled into hydrogels through noncovalent interactions. This hydrogel shows excellent stability, sustained release and reversible stimuli-responses. The hydrogel consists of a three-dimensional nanofiber network that prevents premature degradation. Moreover, it easily enters cells and binds to toll-like receptor 4. This enables rhein hydrogels to significantly dephosphorylate IκBα, inhibiting the nuclear translocation of p65 at the NFκB signalling pathway in lipopolysaccharide-induced BV2 microglia. Subsequently, rhein hydrogels alleviate neuroinflammation with a long-lasting effect and little cytotoxicity compared to the equivalent free-drug in vitro. This study highlights a direct self-assembly hydrogel from natural small molecule as a promising neuroinflammatory therapy.

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Recent evidences show that nervous system acts as a crucial part of cancer microenvironment. Infiltration of nerve fibers into cancer microenvironment has an important active role in cancer progression. The stimulations of both cancer growth and metastasis by members of nervous system such as neurons and glial cells have been demonstrated. However, how the nervous system is built in cancer is largely unknown. Here we show that a fraction of cancer stem cells (CSCs) derived from patients with gastric carcinoma and colorectal carcinoma are capable of producing neurons that are involved in tumor neurogenesis and tumor growth. Cancer stem cell monoclone derived from a single cancer stem cell was able to generate neurons including sympathetic and parasympathetic neurons to take part in the nervous system in cancer tissues. Knocking down the neural cell generating capability of the human CSCs inhibited the growth of xenograft tumors in mouse model. Our data demonstrate that human CSCs are able to produce one of most important components in the cancer microenvironment that are required for cancer development and progression.

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