chlorophyll-a and Squamous-Cell-Carcinoma-of-Head-and-Neck

Photodynamic therapy has attracted significant attention due to its localized treatment advantage. However, the non-specific distribution of photosensitizers and the subsequent potential toxicity caused by sunshine exposure hinder its wide adoption in cancer treatment. To minimize these unwanted effects and improve its efficacy, we developed a bioactivatable self-quenched nanogel, which remains in its inactive state in healthy tissues. Anti-EGFR Affibody decorated nanogels can effectively target head and neck cancer and release activated pheophorbide A in a reducing environment, such as in the tumor stroma and cytoplasm. Consequently, the EGFR targeted nanogel coupled with NIR irradiation alleviates tumor burden by 94.5% while not inducing systemic toxicity.

Topics: Animals; Cell Line, Tumor; Cell Proliferation; Cell Survival; Chlorophyll; ErbB Receptors; Head and Neck Neoplasms; HeLa Cells; Humans; Ligands; Mice; Molecular Targeted Therapy; Nanogels; Photochemotherapy; Radiation-Sensitizing Agents; Squamous Cell Carcinoma of Head and Neck; Xenograft Model Antitumor Assays

To investigate the effect and potential mechanisms about apoptosis induction and migration suppression of photodynamic therapy with a new photosensitizer, 9-hydroxypheophorbide-α (9-HPbD), and diode laser on HN-3 human laryngeal squamous cancer cells.. The attached HN-3 cancer cells were photosesitized with 0.29 μg/ml and 0.59 μg/ml 9-HPbD for 6 h and irradiated by 664 nm diode laser for 15 min at an energy density of 2.0 J/cm for activating 9-HPbD. Wound healing assay and photographing was respectively performed immediately after laser irradiation. Photographing focusing on the same location was repeated 12 h, 24 h and 36 h after PDT and cells migration distance counted respectively. H2DCFDA staining was used to assess accumulation of reactive oxygen series (ROS) 1 h after PDT. MTT assay, Hoechst33342/PI double staining, western blotting were respectively performed to assess cellular viability, apoptosis and the expression of Enos, p-c-Jun, EGFR.. Phototoxicity and apoptosis on HN-3 cells induced by 9-HPbD-PDT was exhibited in a dose-related manner. Neither 9-HPbD alone nor laser alone was cytotoxic to HN-3 cells. Generation of ROS was initiated immediately after PDT. The apoptotic cells, marked with condensed/fragmented blue or pink nuclei, and up-regulated expression of eNOS, p-c-Jun were subsequently induced 24 h after PDT. Coupled with a down-regulated expression of EGFR, a photosensitizer dose-ralated cell migration suppression was initiated by PDT. After pretreatment of GSH or ascorbic acid, a kind of antioxidant, the efficacy of PDT-induced apoptosis and migration suppression was partially inhibited.. Activation of p-c-Jun, eNOS and down-regulated expression of EGFR may respectively involve in the apoptosis induction and cell migration suppression after 9-HPbD-PDT. Generation of ROS may play an important role in the course of apoptosis induction and migration suppression of HN-3 cells initiated by 9-HPbD-PDT.

Topics: Apoptosis; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Movement; Cell Survival; Chlorophyll; Head and Neck Neoplasms; Humans; Laryngeal Neoplasms; Lasers; Photochemotherapy; Photosensitizing Agents; Squamous Cell Carcinoma of Head and Neck