demonstrated the antitumor effect of GNPs encapsulating indocyanine green ICG and DOX in breast cancer.
designed a new way to improve targeting delivery efficiency and treatment outcome of glioma by loading gold NPs into gelatin NPs (GNPs) and decorating with doxorubicin (DOX) and Cy5.5. By loading with different drugs, gelatin NPs can play different role in inhibiting or diagnosing various cancers. Previous studies demonstrated that gelatin-based NP can be used as MMP responsive carrier for tumor cell imaging in cancer treatment. Among the various gelatinases that overexpressed in tumor microenvironment, matrix metalloproteinase (MMP) has been demonstrated to have a promising effect in enriching gelatin NPs. Gelatin, the earliest proteinaceous material in formation of NPs and the carriage of drug through intravenous infusion, exhibits excellent characteristics such as biocompatibility, biodegradability, non-immunogenicity and safety in medical using, can be degraded by gelatinase and ease of bridge.
Among them, nanomaterial-based drug carriers such as liposomes, polymer, inorganic and hybrid protein-inorganic nanoparticles (NPs) have been developed as nanocarriers to deliver various drugs, e.g., chemical anti-tumor drugs, enzymes, antibody, siRNA, noble metal in order to improve the therapeutic effect. So far, various nanomaterials have used in multiple fields including tumor treatment. Nanotechnology demonstrated significant potential to reduce the side effects and increase drug targeting of immunotherapy. However, due to the dysfunction caused by surgery and the chemotherapy resistance, the outcome of HNSCC treatment strategies is usually accompanied by cancer recurrence, metastasis and poor prognosis, and the overall survival rate in past three decades has improved modestly. Generally, current standard therapy of HNSCC still relies on surgery followed by conventional chemotherapy and radiotherapy. HNSCC is one of the most life-affecting malignant diseases, and except the deaths directly caused by HNSCC, the rate of suicide in HNSCC survivors (63.4 per 100,000 person-years) has been the second among all kinds of cancer. Graphical AbstractĪs the sixth most common cancer around the world, there are more than 930,000 new patients of head and neck squamous cell carcinomas (HNSCCs) in 2020, which account for about 90% of head and neck cancer patients.
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. Based on two HNSCC mouse models, we demonstrated that Gel-N-ICG significantly delayed tumor growth without any appreciable body weight loss. 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. In the tumor tissue, Gel-N-ICG nanoparticle was degraded and encapsulated ICG and NSC were effectively released.
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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. 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).
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