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

Abstract

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.

Nanodrug delivery materials for digestive system diseases

“…Scientists are investigating the way that drugs are packaged and wrapped for more precise delivery, as well as their regulated release. As an illustration, Tian et al 60 presented an oral polymeric adsorbent with a supramolecular pattern (called SPORA-SN9) that prevented GI mucositis and microbial dysbiosis brought on by chemotherapy by selectively removing chemotherapeutic drugs from the GI tract, improving the synergy between chemotherapy and immunotherapy.…”

Polymer Nanoantidotes

“…For example, Tian et al performed screening experiments to determine the most effective supramolecular host for complementary interaction with the chemotherapeutic agents doxorubicin (DOX) and irinotecan (IRI) (Figure 2A). [13] Both drugs contain a positively charged amine moiety coupled with a hydrophobic structure for interaction with the negatively charged carboxyl groups and hydrophobic carbocycle parts, respectively, of a supramolecular host. An orally administered polymer nanoantidote (SPORA-SN9) was prepared by crosslinking the supramolecular host (Figure 2B) to enhance the anticancer efficacy while protecting the gastrointestinal tract (Figure 2C, D).…”

Recent Progress of Supramolecular Chemotherapy Based on Host–Guest Interactions

“…[26] It is a multidisciplinary field, mainly based on interactions between molecules, that is, the combination of two or more constituent units connected by non-covalent interactions. [27][28][29][30] Dynamic and reversible non-covalent interactions conferred outstanding stimuli-responsive features and infinite potential to supramolecular architectures. [31][32][33][34] This dynamic binding property enables supramolecular drug delivery systems to induce the release of guest molecules in a controlled manner through unique stimulated conditions, such as pH, light, temperature, ions, ultrasound, and external magnetic fields.…”