A Transformable Mucoadhesive Microgel Network for Noninvasive Multimodal Imaging And Radioprotection of a Large Area of the Gastrointestinal Tract.

The lack of noninvasive imaging and modulation of a large area of the gastrointestinal (GI) tract constrain the diagnosis and treatment of many GI-related diseases. Recent advances use novel mucoadhesive materials to coat a part of the GI tract and then modulate its functions. High mucoadhesion is the key factor of the partial coating, but also the limitation for not spreading and covering the lower GI tract. Here, a bismuth-pectin organic-inorganic hybrid complex is screened and engineered into a transformable microgel network (Bi-GLUE) with high flowability and mucoadhesion, such that it can quickly transit through and coat a large area of the GI tract. In murine and porcine models, Bi-GLUE delivers contrast agents to achieve real-time, large-area GI-tract imaging under X-ray or magnetic resonance  modalities and to facilitate the non-invasive diagnosis of familial adenomatous polyposis. Moreover, Bi-GLUE, like an intracorporal radiation shield, decreases the radiotoxicity in a whole-abdomen irradiation rat model. This transformable microgel network offers a new direction that can modulate a large area of the GI tract and may have broad applications for GI-related conditions.

Oral Supramolecular Adsorbent for Preventing Chemo-Induced Gastrointestinal Mucositis and Microbial Dysbiosis and for Enhancing Chemoimmunotherapy.

The addition of immune checkpoint blockade (ICB) to cytotoxic chemotherapy has emerged as the first-line treatment for multiple cancers. Paradoxically, cytotoxic chemotherapy may limit the therapeutic potential of ICB by significantly impairing the largest immune organ, the gastrointestinal (GI) tract, and driving gut microbial dysbiosis. Here, an orally administered polymeric adsorbent containing a supramolecular motif (named SPORA-SN9) is reported, which can selectively remove chemotherapeutics from the GI tract, thereby preventing chemotherapy-induced GI mucositis and microbial dysbiosis and providing better chemoimmunotherapy synergy. By theoretical design and experimental screening of the molecular recognition motifs, SPORA-SN9 exhibits superior complexation capacity for doxorubicin and irinotecan and high selectivity over a range of commonly used combinational medications. In mouse models of chemotherapy-induced GI mucositis, SPORA-SN9 protects the integrity of the GI tissues and the homeostasis of the gut microbiota. Finally, the addition of SPORA-SN9 enhances the efficacy of chemoimmunotherapy in tumor-bearing mice. SPORA-SN9 offers a translational approach for supramolecular chemistry to modulate complex biosystems by selectively removing target substrates from the GI tract.