The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China.
Department of Oral & Maxillofacial-Head & Neck Oncology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China.
J Nanobiotechnology. 2021 Nov 21;19(1):379. 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.
基质金属蛋白酶（MMP）2 和 9 是蛋白酶家族的成员，通常在肿瘤中上调以增强肿瘤细胞的侵袭和转移，并与头颈部鳞状细胞癌（HNSCC）的不良预后相关。在本工作中，MMP 可降解明胶纳米颗粒（GNPs）同时负载光热剂吲哚菁绿（ICG）和信号转导转录激活因子 3（STAT3）抑制剂 NSC74859（NSC，N），用于高效光热治疗（PTT）和 HNSCC 的免疫治疗。在肿瘤组织中，Gel-N-ICG 纳米颗粒被降解，包裹的 ICG 和 NSC 被有效释放。在近红外（NIR）照射下，释放的 ICG 纳米颗粒能够有效地进行光热破坏肿瘤，而 STAT3 抑制剂 NSC 引发了强烈的抗肿瘤免疫反应，增强了癌症治疗效果。基于两种 HNSCC 小鼠模型，我们证明了 Gel-N-ICG 可显著延迟肿瘤生长，而体重无明显减轻。综上所述，该研究报道的策略可能表明，刺激响应性蛋白酶触发的纳米平台可以通过 PTT 和免疫治疗的联合，更有效地减少复杂肿瘤微环境（TME）中的肿瘤大小。
