Speakers - 2026

Title: Engineered exosome liposome nanovesicles enable car macrophage therapy for radiotherapy induced oral mucositis

Abstract

Radiotherapy-induced oral mucositis (RTOM) remains one of the most debilitating complications in patients receiving head and neck radiotherapy. Nearly all patients develop painful oral ulcers, leading to impaired nutrition, increased infection risk, and interruption of cancer treatment. Current therapies, including rinses, analgesics, and epithelial repair agents, are largely palliative and fail to address the underlying mechanism of persistent inflammation. Our study identifies extracellular calreticulin (CRT), exposed during radiation-induced immunogenic cell death, as a key driver of unresolved inflammation. Inefficient clearance of CRT-positive dying cells leads to chronic immune activation and impaired mucosal repair. We hypothesized that engineering macrophages with a CRT-targeting chimeric antigen receptor (CAR) could enhance efferocytosis, resolve inflammation, and promote mucosal healing. We first established in vitro and in vivo RTOM models to confirm CRT exposure and its association with inflammatory imbalance. We then fabricated hybrid liposome–exosome nanovesicles (HLENs-CAR) that efficiently delivered a CRT-targeting CAR plasmid into macrophages. These artificial exosomes retained the transfection efficiency of cationic liposomes while providing improved biocompatibility. Functionally, CAR-macrophages displayed enhanced phagocytosis and activation of the IL-4/Gas6/STAT6 pathway, promoting pro-resolving phenotypes. To achieve localized release, we embedded HLENs-CAR into a ROS-responsive microneedle hydrogel system (PT MN@HLENs-CAR). This platform degraded rapidly under oxidative stress, releasing the therapeutic vesicles at the injury site. In RTOM mouse models, the microneedle treatment reduced ROS levels, shifted macrophages from M1 to M2, and accelerated mucosal healing. This work demonstrates a mechanism-driven, localized therapy for RTOM. By targeting CRT with engineered macrophages delivered via ROS-responsive microneedles, we provide a novel therapeutic concept with strong translational potential for managing radiotherapy complications.

The audience take away from presentation:

• Mechanistic insight into extracellular calreticulin (CRT) as a driver of persistent inflammation in radiation-induced oral mucositis.
• A demonstration that hybrid liposome–exosome nanovesicles (HLENs) can efficiently deliver CAR plasmids while maintaining the transfection capacity of cationic liposomes.
• Proof-of-concept that a ROS-responsive microneedle hydrogel system enables localized, inflammation-triggered release of engineered vesicles.
• A translational framework for a mechanism-based, localized therapeutic strategy against RTOM.