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NK Cell-Derived Small Extracellular Vesicles Armed With CLDN4-Targeting Peptides Potentiate Radiotherapy in Gastric
Anqi Dong1, Wenhao Shen2, Xiaochun Shen3
1Department of Pathology, the First Affiliated Hospital, State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection & School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Cancer Institute, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, China.
Researchers developed NESC, a novel nanoparticle, to target Claudin-4 (CLDN4) in gastric cancer (GC). This targeted therapy enhances radiosensitization and suppresses tumor growth, offering a new approach for GC treatment.
Area of Science:
- Oncology
- Biomaterials Science
- Nanotechnology
Background:
- Gastric cancer (GC) remains a leading cause of cancer mortality worldwide.
- Late diagnosis and treatment resistance limit current therapeutic options for GC.
- Effective targeted delivery systems are crucial for improving GC treatment outcomes.
Purpose of the Study:
- To identify a specific molecular target for gastric cancer therapy.
- To develop an innovative targeted nano-therapeutic biomaterial for GC.
- To evaluate the efficacy of the developed therapeutic in preclinical models.
Main Methods:
- Analysis of single-cell RNA sequencing datasets to identify overexpressed targets in GC.
- Engineering of natural killer cell-derived small extracellular vesicles (NK-sEVs) into a targeted nanoparticle (NESC) with a CLDN4-targeting peptide.
- Utilizing patient-derived organoid models and xenograft models for functional validation and efficacy assessment.
Main Results:
- Claudin-4 (CLDN4) was confirmed as a highly overexpressed target in GC malignant cells.
- NESC demonstrated precise tumor-specific accumulation and targeting.
- NESC exhibited intrinsic radiosensitizing properties, significantly enhanced by the targeting peptide, leading to robust tumor suppression.
Conclusions:
- The study establishes a versatile framework for developing targeted small extracellular vesicle (sEV)-based therapeutics.
- NESC shows significant potential as a targeted radiosensitizing agent for gastric cancer.
- This research provides a translational foundation for future clinical applications in GC management.
