Purpose: Head and neck cancers develop mainly in the human oral cavity, larynx, hypopharynx, and sinonasal area. Squamous cell carcinoma (SCC) is the major type of head and neck cancer. Current methods for human head and neck cancers treatments are surgery, chemotherapy and radiotherapy. New modality is photodynamic therapy, a noninvasive alternative for oral cancer therapy.
Methods: A novel photosensitizer, pyropheophorbide, was first constructed in nanoparticles, for photodynamic therapy. EGFR silencing RNA was encapsulated into nanoparticles to silence EGFR expression. Two treatments were combined for cancer treatment. EGFR silence RNA and pyropheophorbide nanoparticles were 40.and 25nm in size, respectively. In vitro and in vivo studies were conducted using photodynamic therapy combined with EGFR gene therapy to examine cancer inhibition. Two types of head and neck SCC xenografted nude mice were used to verify therapeutic efficacy.
Results: In vitro and in vivo studies indicated photodynamic therapy combined with EGFR gene therapy showed significant inhibition of cancer growth. The siRNA+PDT group showed significantly reduced tumor volume compared to the untreated (control) group in two human oral carcinoma tumor models. The EGFR siRNA+photodynamic therapy group of human oral carcinoma tumor volumes were reduced by 180~200% compared to the PBS group in 2 models. Combined therapy showed significant tumor volume reduction compared to PBS, scramble siRNA, or photodynamic group. Western blot results confirmed EGFR protein knockdown in the combined treatment group. In addition, no toxic effects were found in both serum biomarkers and major organs of animal.
Conclusion: Results suggest that the novel combination therapy with pyropheophorbide and siEGFR nanoparticles could be a potential treatment to develop for human head and neck cancer in the future.
Chia-Hsien Yeh– Research Assistant, Chung Yuan Christian University, Chungli
Juan Chen– Princess Margaret Cancer Center
Gang Zheng– Princess Margaret Cancer Center
Leaf Huang– Fred Eshelman Distinguished Professor, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill