Effect and underlying mechanism of a photochemotherapy dual-function nanodrug delivery system for head and neck squamous cell carcinoma

• Published in: Journal of translational medicine 2024-11, Vol.22 (1), p.1043-17, Article 1043
• Main Authors: Lin, Qian, Liu, Hui-Min, Wu, Li-Zhi, Yu, Dong-Dong, Hua, Cheng-Yu, Zou, You, Jiao, Wo-Er, Li, Xiang-Pan, Chen, Shi-Ming
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - drug effects; Cancer; Care and treatment; Cell Line, Tumor; Cell Movement - drug effects; Cell Proliferation - drug effects; Demographic aspects; Development and progression; Doxorubicin - pharmacology; Doxorubicin - therapeutic use; Drug Delivery Systems; Epithelial-Mesenchymal Transition - drug effects; Head and neck cancer; Head and Neck Neoplasms - drug therapy; Head and Neck Neoplasms - pathology; Head and neck squamous cell carcinoma; Humans; JNK signalling pathway; MAP Kinase Signaling System - drug effects; Methods; Mice, Inbred BALB C; Mice, Nude; Nanomedicine; Neoplasm Invasiveness; Patient outcomes; Photochemotherapy; Relapse; Squamous Cell Carcinoma of Head and Neck - drug therapy; Squamous Cell Carcinoma of Head and Neck - pathology; Squamous Cell Carcinoma of Head and Neck - therapy; Xenograft Model Antitumor Assays
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-024-05855-8

The novel nanomaterials PNA-TN (PN) and PNA-TN-Dox (PND) have been shown to have strong inhibitory effects on breast cancer; however, it is unclear whether PN and PND have anti-head and neck squamous cell carcinoma (HNSCC) activity, and their potential mechanisms of activity are unknown. So, our study aims to explore the therapeutic effects of PN and PND on HNSCC and their possible mechanisms. We used a series of phenotypic research to evaluate the effects of PN + Laser (L) and PND + L on the biological function of HNSCC cells in vitro and in vivo. We subsequently used mechanism research to examine changes in mRNA and protein expression related to apoptosis, epithelial‒mesenchymal transition (EMT), and the JNK signalling pathway. Our study revealed that PN and PND have strong inhibitory effects on HNSCC cells both in vitro and in vivo. In vitro, PN and PND significantly inhibited the proliferation, migration, invasion and EMT ability of HNSCC cells and promoted apoptosis; the inhibitory effect in the PND + L group was significantly greater than that in the PN + L group. In vivo, both treatments led to significant reductions in tumour volume and weight. Notably, the tumour volume and weight in the PND + L group were significantly lower than those in the PN + L group. Mechanism research confirmed that PN + L activated the expression of apoptosis-related proteins and inhibited the expression of EMT-related proteins via the JNK pathway. Furthermore, the anti-HNSCC effect of PN + L was blocked after the use of a JNK pathway inhibitor. Treatment with PN + L or PND + L significantly inhibited the malignant progress of HNSCC cells, and the therapeutic effect of PND + L was significantly stronger than that of PN + L. The JNK signalling pathway is a key mechanism by which PN exerts its anti-HNSCC activity.