{"title":"Enhanced photothermal therapy for oral cancer using benzothiadiazole-based nanoparticle-loaded hydrogels.","authors":"Zi Fu, Ling Huang, Xinyu Zhang, Zhichao Zheng, Lihong Wu, Huade Zheng","doi":"10.1080/21691401.2025.2540648","DOIUrl":null,"url":null,"abstract":"<p><p>Recent advances in photothermal therapy (PTT) using nanoparticles (NPs), particularly benzothiadiazole-based agents, offer promising strategies for targeted cancer treatment with enhanced efficacy and reduced side effects. However, challenges such as poor stability and limited retention at the tumour site persist, necessitating the development of advanced delivery systems to optimize the effectiveness of these NPs in clinical applications. In this study, we synthesized a benzothiadiazole-based photothermal small molecule, BPD-BBTD NPs, with a median particle size of 116 nm. And subsequently incorporated them into a chitosan (CS) and hydroxyethyl cellulose (HEC) matrix to form a novel hydrogel, BPD-BBTD NPs @CS-HEC. The photothermal efficacy of both the NPs and the hydrogel against oral squamous cell carcinoma (OSCC) was further explored. The photothermal conversion efficiency of BPD BBTD NPs small molecules can reach 40%. When the concentration is 400 μg/mL, the temperature can reach 75 °C after 3 min of NIR irradiation. The hydrogel's dense network structure was designed to effectively retain heat within its matrix, thus enhancing the photothermal effect and reducing heat dissipation. Our <i>in vitro</i> experiments demonstrated that BPD-BBTD NPs significantly inhibited the proliferation and migration of OSCC cells while exerting minimal cytotoxic effects on normal cells. The survival rates of mouse fibroblasts (L929) and human oral keratinocytes (Hok) were over 80%. Mechanistic investigations indicated that under near-infra-red (NIR) light irradiation, the NPs increased the production of reactive oxygen species (ROS) in OSCC cells. This ROS upregulation further led to apoptosis in OSCC cells, primarily through the reduction of mitochondrial membrane potential, a consequence of heat stress induced by NIR irradiation. Furthermore, the anti-tumour efficacy of BPD-BBTD NPs @CS-HEC hydrogel was validated using an <i>in situ</i> mouse model of OSCC. Furthermore, the relative change rate of tumour volume before and after treatment was reduced by 94.4%. In conclusion, our findings suggest that BPD-BBTD NPs @CS-HEC hydrogels, under the activation of NIR light, represent a promising biomaterial for the targeted treatment of OSCC, offering a synergistic approach by combining PTT with localized, sustained treatment delivery.</p>","PeriodicalId":8736,"journal":{"name":"Artificial Cells, Nanomedicine, and Biotechnology","volume":"53 1","pages":"345-360"},"PeriodicalIF":4.5000,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Artificial Cells, Nanomedicine, and Biotechnology","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1080/21691401.2025.2540648","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/7/31 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Recent advances in photothermal therapy (PTT) using nanoparticles (NPs), particularly benzothiadiazole-based agents, offer promising strategies for targeted cancer treatment with enhanced efficacy and reduced side effects. However, challenges such as poor stability and limited retention at the tumour site persist, necessitating the development of advanced delivery systems to optimize the effectiveness of these NPs in clinical applications. In this study, we synthesized a benzothiadiazole-based photothermal small molecule, BPD-BBTD NPs, with a median particle size of 116 nm. And subsequently incorporated them into a chitosan (CS) and hydroxyethyl cellulose (HEC) matrix to form a novel hydrogel, BPD-BBTD NPs @CS-HEC. The photothermal efficacy of both the NPs and the hydrogel against oral squamous cell carcinoma (OSCC) was further explored. The photothermal conversion efficiency of BPD BBTD NPs small molecules can reach 40%. When the concentration is 400 μg/mL, the temperature can reach 75 °C after 3 min of NIR irradiation. The hydrogel's dense network structure was designed to effectively retain heat within its matrix, thus enhancing the photothermal effect and reducing heat dissipation. Our in vitro experiments demonstrated that BPD-BBTD NPs significantly inhibited the proliferation and migration of OSCC cells while exerting minimal cytotoxic effects on normal cells. The survival rates of mouse fibroblasts (L929) and human oral keratinocytes (Hok) were over 80%. Mechanistic investigations indicated that under near-infra-red (NIR) light irradiation, the NPs increased the production of reactive oxygen species (ROS) in OSCC cells. This ROS upregulation further led to apoptosis in OSCC cells, primarily through the reduction of mitochondrial membrane potential, a consequence of heat stress induced by NIR irradiation. Furthermore, the anti-tumour efficacy of BPD-BBTD NPs @CS-HEC hydrogel was validated using an in situ mouse model of OSCC. Furthermore, the relative change rate of tumour volume before and after treatment was reduced by 94.4%. In conclusion, our findings suggest that BPD-BBTD NPs @CS-HEC hydrogels, under the activation of NIR light, represent a promising biomaterial for the targeted treatment of OSCC, offering a synergistic approach by combining PTT with localized, sustained treatment delivery.
期刊介绍:
Artificial Cells, Nanomedicine and Biotechnology covers the frontiers of interdisciplinary research and application, combining artificial cells, nanotechnology, nanobiotechnology, biotechnology, molecular biology, bioencapsulation, novel carriers, stem cells and tissue engineering. Emphasis is on basic research, applied research, and clinical and industrial applications of the following topics:artificial cellsblood substitutes and oxygen therapeuticsnanotechnology, nanobiotecnology, nanomedicinetissue engineeringstem cellsbioencapsulationmicroencapsulation and nanoencapsulationmicroparticles and nanoparticlesliposomescell therapy and gene therapyenzyme therapydrug delivery systemsbiodegradable and biocompatible polymers for scaffolds and carriersbiosensorsimmobilized enzymes and their usesother biotechnological and nanobiotechnological approachesRapid progress in modern research cannot be carried out in isolation and is based on the combined use of the different novel approaches. The interdisciplinary research involving novel approaches, as discussed above, has revolutionized this field resulting in rapid developments. This journal serves to bring these different, modern and futuristic approaches together for the academic, clinical and industrial communities to allow for even greater developments of this highly interdisciplinary area.