Osteosarcoma is one of the most common malignant tumors in children and tends to occur around the knee. Problems such as recurrence and metastasis are the outcomes of traditional treatment methods. One of the reasons for these issues is the infiltration of tumor-associated macrophages (TAMs) in the tumor microenvironment (TME). Photothermal immunotherapy has emerged as one of the most potent approaches for cancer treatment. In this study, we designed a biodegradable, injectable, and photothermal hydrogel that functions to reprogram TAMs into classically activated macrophages (M1) based on hydroxypropyl chitin (HPCH), tannic acid and ferric ions (HTA). We found that HTA had better photothermal efficiency than a pure hydrogel; its photothermal repeatability is good and it can be NIR (808 nm) irradiated as needed. In addition, the precooled hydrogel solution can be injected into the tumor and it can rapidly gel in situ. In vitro, HTA with NIR irradiation (HTA + NIR) induced the apoptosis of K7M2 cancer cells. In vivo, the local administration of HTA + NIR exerted photothermal killing of primary tumors and reprogramming of TAMs into M1-type macrophages in the TME. Therefore, the injectable photothermally active antitumor hydrogel has great potential for modulating the TME to treat bone tumors.

中文翻译：

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生物可降解光热温敏水凝胶通过重编程巨噬细胞治疗骨肉瘤

骨肉瘤是儿童最常见的恶性肿瘤之一，好发于膝关节周围。复发和转移等问题是传统治疗方法的后果。这些问题的原因之一是肿瘤微环境 (TME) 中肿瘤相关巨噬细胞 (TAM) 的浸润。光热免疫疗法已成为最有效的癌症治疗方法之一。在这项研究中，我们设计了一种可生物降解、可注射和光热的水凝胶，其功能是将 TAM 重编程为基于羟丙基几丁质 (HPCH)、单宁酸和铁离子 (HTA) 的经典活化巨噬细胞 (M1)。我们发现 HTA 比纯水凝胶具有更好的光热效率；光热重复性好，可根据需要进行近红外（808nm）照射。此外，原地。在体外，HTA 与 NIR 照射 (HTA + NIR) 诱导 K7M2 癌细胞的凋亡。在体内，HTA + NIR 的局部给药对原发性肿瘤产生光热杀伤，并将 TAM 重编程为 TME 中的 M1 型巨噬细胞。因此，可注射的光热活性抗肿瘤水凝胶具有调节TME治疗骨肿瘤的巨大潜力。