Nanomedicine Journal

Nanomedicine Journal

Research advances of tumor microenvironment-responsive nanomaterials for oral squamous cell carcinoma

Articles in Press

Document Type : Review Paper

Authors
Mengze Wang 1
Xiaoxiao Hu 2
Jianxue Hao 3
Yanming Guo 4
Yongping Ma 1, 4
1 College of Stomatology, North China University of Science and Technology, Tangshan, People’s Republic of China, China
2 Department of Clinical Pharmacy, The No.2 Hospital of Baoding, Baoding, People’s Republic of China, China
3 Department of Orthopaedic Surgery, The No.2 Hospital of Baoding, Baoding, People’s Republic of China, China
4 Department of Stomatology, The No.2 Hospital of Baoding, Baoding, People’s Republic of China, China
10.22038/nmj.2026.95848.2429
Abstract
Introduction: Oral squamous cell carcinoma (OSCC) remains a main cause of morbidity and mortality in patients with head and neck squamous cell carcinoma (HNSC). Despite advances in clinical management, conventional therapeutic approaches are often accompanied by significant trauma and a high risk of recurrence.
Objective(s): The tumor microenvironment (TME) exhibits unique biochemical hallmarks. The rapid advancement of nanotechnology has facilitated the construction of TME-responsive nanoscale drug delivery systems (DDSs).
Materials and Methods: The TME is characterized by acidic pH, elevated glutathione (GSH) levels, dysregulated reactive oxygen species (ROS) metabolism, and overexpression of various tumor-associated enzymes (e.g., matrix metalloproteinases). These distinctive features collectively offer promising molecular targets for the development of targeted therapeutic strategies. The progress of nanotechnology also provides strong support for the construction of TME-responsive DDSs.
Results: While promising precision therapeutic strategies for OSCC continue to emerge, critical gaps remain. Herein, this paper presents a narrative review of TME-responsive DDSs for OSCC treatment, categorizing them by single- and multi-stimuli activation mechanisms and critically assessing the limitations of current nanomaterial-based approaches as well as their future directions.
Conclusion: In conclusion, additional efforts will be required in the future to accelerate the clinical translation of DDSs.
Keywords
Squamous cell carcinoma of head and neck
Tumor microenvironment
Nanostructures
Drug delivery systems
Subjects
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Available Online from 24 October 2026