Related Experiment Video

Updated: Aug 30, 2026

Mechanistic Insight into the Development of TNBS-Mediated Intestinal Fibrosis and Evaluating the Inhibitory Effects of Rapamycin
10:21

Mechanistic Insight into the Development of TNBS-Mediated Intestinal Fibrosis and Evaluating the Inhibitory Effects of Rapamycin

Published on: September 12, 2019

A Receptor-Mediated Endolysosomal Recycling Chimera Enables Catalytic TNF-α Degradation for Sustained Treatment of

Wenxue Xie1, Yuqing Wu2, Xichen Wan2

  • 1Institute of Chemical Biology and Nanomedicine, State Key Laboratory of Chemo and Biosensing, Hunan Provincial Key Laboratory of Biomacromolecular Chemical Biology, College of Chemistry and Chemical Engineering, Hunan University, Changsha, China.

Advanced Materials (Deerfield Beach, Fla.)
|August 28, 2026
PubMed

Mucosal inflammatory disorders such as dry eye disease (DED) and inflammatory bowel disease (IBD), driven by TNF-α-mediated immune-epithelial crosstalk, remain therapeutically challenging. Conventional inhibitors often suffer from poor mucosal permeability and transient efficacy with 1:1 binding. Although extracellular protein degradation (eTPD) technologies can eliminate pathogenic proteins, most of them operate stoichiometrically, limiting dosage efficiency and durability. Here, we report a receptor-mediated endolysosomal recycling chimera (RECYC) platform that enables catalytic, recyclable degradation of TNF-α with multiple turnovers, achieving sustained suppression of mucosal inflammation. RECYC integrates a pH-responsive peptide that binds TNF-α at physiological pH and releases it in acidic endosomes, with a CI-M6PR-targeting aptamer that remains pH-stable to drive continuous recycling. The anti-TNF-α RECYC achieved efficient uptake and recyclable clearance of extracellular TNF-α across conjunctival and colonic epithelial cells and macrophages, achieving superstoichiometric TNF-α clearance with up to 7.5 catalytic turnovers. The ∼30 kDa RECYC exhibited superior tissue penetration in murine cornea and colon compared to inhibitory antibodies. In murine DED and IBD models, RECYC restored ocular surface homeostasis and reduced colon inflammation with low-dose, infrequent administration. Human corneal limbus organoids further confirmed prolonged anti-inflammatory activity. Together, RECYC establishes a modular, recyclable eTPD platform for sustained treatment of TNF-α-driven mucosal inflammation.

Keywords:
aptamer‐peptide chimeracatalytic TNF‐α degradationdry eye diseaseinflammatory bowel diseasemucosal inflammationrecycling chimera

More Related Videos

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity07:09

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity

Published on: January 7, 2019

The Cell-based L-Glutathione Protection Assays to Study Endocytosis and Recycling of Plasma Membrane Proteins09:22

The Cell-based L-Glutathione Protection Assays to Study Endocytosis and Recycling of Plasma Membrane Proteins

Published on: December 13, 2013

Related Concept Videos

Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
Recycling Endosomes and Transcytosis00:58

Recycling Endosomes and Transcytosis

The recycling endosome, also known as the endosomal recycling compartment (ERC), is a part of the slow-recycling process of the endocytic pathway. Molecules internalized through receptor-mediated endocytosis are either degraded in the lysosomes or are recycled to the plasma membrane through the fast- or slow-recycling route.
The recycling endosome is not a single organelle but an extensively tubulated network of recycling pathways. It functions in storing molecules or transporting them across...
Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF01:24

Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF

Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab (Humira),...
Receptor-mediated Endocytosis01:20

Receptor-mediated Endocytosis

Receptor-mediated endocytosis is when bulk amounts of specific molecules are imported into a cell after binding to cell surface receptors. The molecules bound to these receptors are taken into the cell through inward folding of the cell surface membrane, which is eventually pinched off into a vesicle within the cell. Structural proteins, such as clathrin, coat the budding vesicle.
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
Receptor-mediated Endocytosis01:48

Receptor-mediated Endocytosis

Receptor-mediated endocytosis is a process through which bulk amounts of specific molecules can be imported into a cell after binding to cell surface receptors. The molecules bound to these receptors are taken into the cell through inward folding of the cell surface membrane, which is eventually pinched off into a vesicle within the cell. Structural proteins, such as clathrin, coat the budding vesicle and give it its round form.Clathrin-Mediated Endocytosis of LDLOne well-characterized example...
Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...