The synthesis and application of nano doxorubicin- indocyanine green matrix metalloproteinase-responsive hydrogel in chemophototherapy for head and neck squamous cell carcinoma.
Background
Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies, with high rates of mortality and morbidity worldwide. Owing to the special anatomical location of this tumor, an effective, minimally invasive treatment with low systemic toxicity is highly desirable. Hydrogels have shown great potential for tumor-targeting therapy, with excellent performance. However, there have been few reports on co-loading photosensitizers and chemotherapeutic drugs into hydrogels. In this study, we synthesized a nano doxorubicin-indocyanine green matrix metalloproteinase (MMP)-responsive hydrogel (denoted as NDIMH), combining chemotherapy and phototherapy, to achieve superior antitumor efficacy.


Methods
First, NDIMH was synthesized and characterized by scanning electron microscopy and drug-release assays. Second, the photosensitivity properties and antitumor efficiency of this drug delivery system were studied in vivo and in vitro. Last, the imaging and biodistribution of NDIMH were monitored using the Maestro EX in vivo imaging system.


Results
The nanodrugs loaded into the smart hydrogel exhibited uniform size distribution, excellent size stability, and a sustained release in the presence of MMP-2. NDIMH showed ideal photosensitivity characteristics under light. NDIMH with 808 nm near-infrared (NIR) irradiation effectively inhibited the viability, invasion, and metastasis of SCC-15 in vitro. After intratumoral injection of NDIMH with 808 nm NIR illumination, the hydrogels exhibited favorable synergistic antitumor efficacy and acceptable biosafety. Additionally, fluorescence imaging showed that NDIMH could significantly improve the retention of nanodrugs at the tumor site.


Conclusion
The intratumoral injection of NDIMH with 808 nm NIR irradiation could be a promising chemophototherapy alternative for HNSCC.
['Wang|Huan-Huan|HH|', 'Fu|Zhi-Guang|ZG|', 'Li|Wei|W|', 'Li|Yun-Xia|YX|', 'Zhao|Li-Sheng|LS|', 'Wen|Li|L|', 'Zhang|Jian-Jun|JJ|', 'Wen|Ning|N|']
D000818:Animals D000970:Antineoplastic Agents D045744:Cell Line, Tumor D049109:Cell Proliferation D002470:Cell Survival D004317:Doxorubicin D005453:Fluorescence D006801:Humans D020100:Hydrogels D007208:Indocyanine Green D008027:Light D020782:Matrix Metalloproteinases D008807:Mice, Inbred BALB C D008819:Mice, Nude D053758:Nanoparticles D009361:Neoplasm Invasiveness D009362:Neoplasm Metastasis D010778:Photochemotherapy D051381:Rats D000077195:Squamous Cell Carcinoma of Head and Neck D014018:Tissue Distribution
indocyanine green hydrogel chemophototherapy MMP-responsive doxorubicin