Gelatinase-sensitive nanoparticles loaded with photosensitizer and STAT3 inhibitor for cancer photothermal therapy and immunotherapy

• Published in: Journal of nanobiotechnology Vol. 19; no. 1; p. 379
• Main Authors: Bu, Lin-Lin, Wang, Han-Qi, Pan, Yuanwei, Chen, Lei, Wu, Hao, Wu, Xianjia, Zhao, Chenchen, Rao, Lang, Liu, Bing, Sun, Zhi-Jun
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 21-11-2021; BioMed Central; BMC
• Subjects: Animal models; Animals; Body weight; Body weight loss; Cancer; Cancer therapies; Cell Line, Tumor; Cell Survival - drug effects; Chemotherapy; Design and construction; Drug delivery systems; Drug therapy; Drugs; Gelatin; Gelatinase; Gelatinases - metabolism; Head and neck carcinoma; Health aspects; I.R. radiation; Immunotherapy; Indocyanine Green - chemistry; Indocyanine Green - pharmacokinetics; Indocyanine green, STAT3 inhibitor; Inhibitors; Irradiation; Matrix metalloproteinase; Matrix metalloproteinases; Medical prognosis; Metalloproteinase; Metastases; Metastasis; Mice; Nanomaterials; Nanomedicine; Nanoparticles; Nanoparticles - chemistry; Nanoparticles - metabolism; Pharmaceutical research; Photochemotherapy; Photosensitizing Agents - chemistry; Photosensitizing Agents - pharmacokinetics; Photosensitizing Agents - pharmacology; Phototherapy; Photothermal Therapy; Proteases; Protein Inhibitors of Activated STAT - chemistry; Protein Inhibitors of Activated STAT - pharmacokinetics; Protein Inhibitors of Activated STAT - pharmacology; Proteins; Squamous cell carcinoma; Stat3 protein; STAT3 Transcription Factor - antagonists & inhibitors; Stimuli-responsive drug release; Technology application; Therapy; Transcription; Tumor cells; Tumor microenvironment; Tumors; Vehicles; Weight loss; China; Photothermal therapy; Indocyanine green, STAT3 inhibitor; Immunotherapy; Stimuli-responsive drug release
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-021-01125-7

Matrix metalloproteinase (MMP) 2 and 9 are the family members of proteases normally up-regulated in tumor to enhance the invasion and metastatic of tumor cells, and are associated with poor outcome of head and neck squamous cell carcinomas (HNSCCs). In the present work, MMPs-degradable gelatin nanoparticles (GNPs) are simultaneously loaded with photosensitizer indocyanine green (ICG) along with signal transducer activator of transcription 3 (STAT3) inhibitor NSC74859 (NSC, N) for efficient photothermal therapy (PTT) and immunotherapy of HNSCCs. In the tumor tissue, Gel-N-ICG nanoparticle was degraded and encapsulated ICG and NSC were effectively released. Under near-infrared (NIR) irradiation, the released ICG nanoparticles enabled effective photothermal destruction of tumors, and the STAT3 inhibitor NSC elicited potent antitumor immunity for enhanced cancer therapy. Based on two HNSCC mouse models, we demonstrated that Gel-N-ICG significantly delayed tumor growth without any appreciable body weight loss. Taken together, the strategy reported here may contribute that the stimuli-responsive proteases triggered nanoplatform could reduce tumor size more effectively in complex tumor microenvironment (TME) through combination of PTT and immunotherapy.