Smart biodegradable hydrogels incorporating a photoactive Ir(III) complex for NIR-triggered oral cancer treatment

Abstract Background Oral squamous cell carcinoma (OSCC) is the most common cancer in the head and neck region, accounting for nearly 90% of oral cavity tumors. OSCC cells often overexpress epidermal growth factor receptor (EGFR), which is linked to tumor formation, progression, and differentiation....

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Main Authors: Fang Yang, Ning Luo, Lizhen Ren, Wei Ding, Xuesong Wu
Format: Article
Language:English
Published: BMC 2025-07-01
Series:Cancer Nanotechnology
Subjects:
Online Access:https://doi.org/10.1186/s12645-025-00336-z
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author Fang Yang
Ning Luo
Lizhen Ren
Wei Ding
Xuesong Wu
author_facet Fang Yang
Ning Luo
Lizhen Ren
Wei Ding
Xuesong Wu
author_sort Fang Yang
collection DOAJ
description Abstract Background Oral squamous cell carcinoma (OSCC) is the most common cancer in the head and neck region, accounting for nearly 90% of oral cavity tumors. OSCC cells often overexpress epidermal growth factor receptor (EGFR), which is linked to tumor formation, progression, and differentiation. Surgery and chemotherapy are the main treatments for OSCC, but they are ineffective compared to other oral cancers. Method To overcome these restrictions, anticancer-active Ir(III) complex-based photosensitizers are incorporated into a PANI-PEG-CS hydrogel and delivered to tumorous tissue, where they are activated by near-infrared (NIR) light to combat cancer. Results Hydrogels incorporating Ir(III) complex could be ingested by OSCC cells under NIR irradiation and have shown strong selectivity toward mitochondria. Further investigations confirmed that Ir increased ROS formation, decreased mitochondrial membrane potential, and depleted ATP levels, all of which led to OSCC cell apoptosis at 62.5 µg/ml. Western blot analysis showed that Ir(III)@PANI-PEG-CS hydrogel induces apoptosis in CAL-27 cells by activating the mitochondria-dependent apoptotic pathway and the PI3K/AKT pathway. Conclusion Nanocomposites selectively accumulate in malignant cells and effectively eliminate them using NIR irradiation. We conclude that complex Ir(III)@PANI-PEG-CS hydrogel may be a promising candidate for new anticancer therapies. Graphical Abstract
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spelling doaj-art-6d67be2cb54c43d0b655477115dabbc02025-08-20T03:42:44ZengBMCCancer Nanotechnology1868-69581868-69662025-07-0116112010.1186/s12645-025-00336-zSmart biodegradable hydrogels incorporating a photoactive Ir(III) complex for NIR-triggered oral cancer treatmentFang Yang0Ning Luo1Lizhen Ren2Wei Ding3Xuesong Wu4Radiotherapy Department, Head and Neck Disease Area, Shanxi Province Cancer Hospital/ Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical UniversityRadiotherapy Department, Head and Neck Disease Area, Shanxi Province Cancer Hospital/ Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical UniversityShanxi Health Vocational CollegeDepartment of Head and Neck Surgery, Shanxi Cancer Hospital, Shanxi Province Cancer Hospital/ Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical UniversityDepartment of Head and Neck Surgery, Shanxi Cancer Hospital, Shanxi Province Cancer Hospital/ Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical UniversityAbstract Background Oral squamous cell carcinoma (OSCC) is the most common cancer in the head and neck region, accounting for nearly 90% of oral cavity tumors. OSCC cells often overexpress epidermal growth factor receptor (EGFR), which is linked to tumor formation, progression, and differentiation. Surgery and chemotherapy are the main treatments for OSCC, but they are ineffective compared to other oral cancers. Method To overcome these restrictions, anticancer-active Ir(III) complex-based photosensitizers are incorporated into a PANI-PEG-CS hydrogel and delivered to tumorous tissue, where they are activated by near-infrared (NIR) light to combat cancer. Results Hydrogels incorporating Ir(III) complex could be ingested by OSCC cells under NIR irradiation and have shown strong selectivity toward mitochondria. Further investigations confirmed that Ir increased ROS formation, decreased mitochondrial membrane potential, and depleted ATP levels, all of which led to OSCC cell apoptosis at 62.5 µg/ml. Western blot analysis showed that Ir(III)@PANI-PEG-CS hydrogel induces apoptosis in CAL-27 cells by activating the mitochondria-dependent apoptotic pathway and the PI3K/AKT pathway. Conclusion Nanocomposites selectively accumulate in malignant cells and effectively eliminate them using NIR irradiation. We conclude that complex Ir(III)@PANI-PEG-CS hydrogel may be a promising candidate for new anticancer therapies. Graphical Abstracthttps://doi.org/10.1186/s12645-025-00336-zOral squamous cell carcinomaNear-infrared lightMitochondriaIridium(III) complexHydrogel
spellingShingle Fang Yang
Ning Luo
Lizhen Ren
Wei Ding
Xuesong Wu
Smart biodegradable hydrogels incorporating a photoactive Ir(III) complex for NIR-triggered oral cancer treatment
Cancer Nanotechnology
Oral squamous cell carcinoma
Near-infrared light
Mitochondria
Iridium(III) complex
Hydrogel
title Smart biodegradable hydrogels incorporating a photoactive Ir(III) complex for NIR-triggered oral cancer treatment
title_full Smart biodegradable hydrogels incorporating a photoactive Ir(III) complex for NIR-triggered oral cancer treatment
title_fullStr Smart biodegradable hydrogels incorporating a photoactive Ir(III) complex for NIR-triggered oral cancer treatment
title_full_unstemmed Smart biodegradable hydrogels incorporating a photoactive Ir(III) complex for NIR-triggered oral cancer treatment
title_short Smart biodegradable hydrogels incorporating a photoactive Ir(III) complex for NIR-triggered oral cancer treatment
title_sort smart biodegradable hydrogels incorporating a photoactive ir iii complex for nir triggered oral cancer treatment
topic Oral squamous cell carcinoma
Near-infrared light
Mitochondria
Iridium(III) complex
Hydrogel
url https://doi.org/10.1186/s12645-025-00336-z
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