Monocyte Backpack Delivery of Engineered MCF‐7 Exosomes for the Treatment of Early Stage Type 1 Diabetes

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disorder characterized by autoimmune‐mediated destruction of pancreatic β‐cells through cytotoxic T lymphocyte infiltration, leading to absolute insulin deficiency. Supplementation of exogenous insulin can't protect remaining β‐cells or address the root autoimmune cause. The emerging therapeutic strategies focus on immunomodulatory approaches, targeting the activation of the programmed death 1/programmed death ligand 1 (PD‐1/PD‐L1) pathway could attenuate T cell‐mediated β‐cell destruction, thereby alleviating inflammation in early‐stage T1DM. However, nonselective PD‐1/PD‐L1 blockade can cause toxicity. Herein, exosomes from PD‐L1 high MCF‐7 cells are utilized, modified with monocyte‐targeting IgG, and have their contents removed via electroporation to eliminate tumorigenicity. Monocytes have the characteristic of targeting inflammatory sites. rExo‐IgG is stably anchored to the monocytes’ membrane through IgG and transported as a backpack of monocytes to the inflammatory sites (pancreas and wounds). In the pancreatic tissue, rExo‐IgG through PD‐1/PD‐L1 pathway, inhibiting their activation and protecting β‐cells. At the site of tissue injury, rExo‐IgG repolarizes macrophages from pro‐inflammatory M1 to anti‐inflammatory M2. It also promotes fibroblast proliferation and migration, enhancing tissue regeneration. This dual‐targeting exosome platform not only exhibits therapeutic efficacy against early‐stage T1DM but also offers a novel strategy for the treatment of diabetic wound healing disorders.