Recent Advances in Nanomedicine for Targeted Phototherapy in Head and Neck Cancer

Hongshuai Liu,1,2 Chen Lin,1,2 Wenying Li,3 Linrong Wu,1,2 Zihao Xia,1,2 Yi Wu,1,2 Yanqi Huang,1,2 Shanshan Gu,1,2 Junjun Zhang,4 Zhisen Shen1,2 1Department of Otolaryngology-Head and Neck Surgery, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, Zhejiang, People’s Republic of China; 2Ningbo Key Laboratory of Digital Medicine Precision Diagnosis and Treatment of Otorhinolaryngology, Head and Neck Diseases, Ningbo, People’s Republic of China; 3School of Materials Chemistry and Chemical Engineering, Ningbo University, Ningbo, Zhejiang, People’s Republic of China; 4Ningbo Hospital of Integrated Traditional Chinese and Western Medicine, Ningbo, People’s Republic of ChinaCorrespondence: Junjun Zhang, Email 15267855085@163.com Zhisen Shen, Email szs7216@163.comAbstract: Head and neck cancer is the seventh most common malignancy worldwide. Conventional treatments, including surgery, chemotherapy, radiotherapy, and immunotherapy, have achieved substantial clinical success. However, their efficacy remains limited due to treatment-associated toxicity and suboptimal therapeutic outcomes. Phototherapy, encompassing photodynamic therapy (PDT) and photothermal therapy (PTT), has emerged as a promising anticancer strategy owing to its high selectivity, minimal invasiveness, and low systemic toxicity. These modalities exert antitumor effects through distinct yet complementary mechanisms. PDT utilizes a photosensitizer activated by light of a specific wavelength to generate reactive oxygen species, thereby inducing cytotoxicity. In contrast, PTT employs photothermal agents to convert light energy into heat for tumor ablation. With advances in photosensitizer design, nanotechnology, and immunotherapy, phototherapy has gained increasing attention as a potential alternative for the treatment of head and neck cancer. In this review, we provide a concise overview of the fundamental principles and mechanisms of PDT and PTT, and present recent progress in smart phototherapeutic agents. For example, liposome-based biomimetic nanodelivery systems enable precise regulation of biodistribution and release kinetics, while carbon-based materials and hybrid nanostructures have attracted considerable interest due to their multifunctionality and applicability in both PDT and PTT. Moreover, we discuss recent applications of PTT/PDT in combination with chemotherapy, immunotherapy, radiotherapy, and gene therapy for head and neck cancer. We also summarize progress regarding agents approved by the U.S. Food and Drug Administration (FDA) and ongoing clinical trials. Finally, we highlight the major challenges and future directions for the broader clinical translation of nanomedicine-based targeted phototherapy. The illustration consists of three main sections. The first section shows a circular diagram labeled ’Combination therapy for HNC’ with segments representing various therapies such as chemotherapy, radiotherapy, gene therapy and others. The second section depicts commonly used nanomedicines, including chitosan, rose bengal, porphyrin and gold nanoparticles, among others. The third section illustrates types of cell death, including necrosis, apoptosis, pyroptosis, necroptosis and autophagy, with detailed pathways involving cell membrane, mitochondria, ER and DNA. The central image shows a human head and neck with labeled areas like nasopharynx, oropharynx and thyroid, indicating the application of laser therapy targeting cancer cells.Illustration of combination therapy for HNC, nanomedicines and types of cell death.Keywords: nanoparticles, photodynamic therapy, photothermal therapy