长效纳米混合水凝胶诱导持续免疫原性化疗,抑制术后肿瘤复发和转移。
Long-Acting Nanohybrid Hydrogel Induces Persistent Immunogenic Chemotherapy for Suppressing Postoperative Tumor Recurrence and Metastasis.
发表日期:2023 Nov 09
作者:
Yaoqi Li, Jie Zhu, Yifan Yang, Yitian Chen, Lishan Liu, Jing Tao, Huabing Chen, Yibin Deng
来源:
Cellular & Molecular Immunology
摘要:
尽管手术切除技术不断进步,但术后肿瘤复发和转移仍然是一个巨大的挑战。在这里,我们构建了一种可注射的姜黄素/阿霉素负载纳米颗粒(NanoCD)水凝胶,它可以通过重塑肿瘤免疫微环境(TIME)有效抑制肿瘤再生和转移,从而实现高效的术后癌症治疗。 NanoCD 是在人血清白蛋白存在下通过 π-π 堆积和氢键控制姜黄素 (CUR) 和阿霉素 (DOX) 组装而制备的。为了促进术后肿瘤的长期治疗,NanoCD被进一步掺入温度敏感的泊洛沙姆407凝胶(NanoCD@Gel)中用于腔内给药。从机制上讲,DOX 诱导细胞内活性氧 (ROS) 的产生,而 CUR 通过抑制硫氧还蛋白还原酶 (TrxR) 来减少 ROS 代谢。 DOX 和 CUR 的协同作用放大了细胞内 ROS 水平,从而导致肿瘤细胞的免疫原性细胞死亡 (ICD) 增强。原位生成的NanoCD@Gel在切除后注射到肿瘤腔内后,可以以受控的方式局部释放CUR和DOX,诱导局部化疗并持续激活抗肿瘤免疫反应,从而实现增强免疫原性化疗并减少全身化疗的效果。毒性。我们的工作提供了一种优雅的策略,可以持续刺激有效的抗肿瘤免疫,以防止术后肿瘤复发和转移。
Despite the continuous advancement of surgical resection techniques, postoperative tumor recurrence and metastasis remain a huge challenge. Here, we constructed an injectable curcumin/doxorubicin-loaded nanoparticle (NanoCD) hydrogel, which could effectively inhibit tumor regrowth and metastasis via reshaping the tumor immune microenvironment (TIME) for highly effective postsurgical cancer treatment. NanoCD was prepared by the controlled assembly of curcumin (CUR) and doxorubicin (DOX) via π-π stacking and hydrogen bonding in the presence of human serum albumin. To facilitate prolonged treatment of postsurgical tumors, NanoCD was further incorporated into the temperature-sensitive Poloxamer 407 gel (NanoCD@Gel) for intracavity administration. Mechanistically, DOX induced the generation of intracellular reactive oxygen species (ROS) and CUR reduced the ROS metabolism by inhibiting thioredoxin reductase (TrxR). The synergy of DOX and CUR amplified intracellular ROS levels and thus resulted in enhanced immunogenic cell death (ICD) of tumor cells. Upon being injected into the tumor cavity after resection, the in situ-generated NanoCD@Gel allowed the local release of CUR and DOX in a controlled manner to induce local chemotherapy and persistently activate the antitumor immune response, thereby achieving enhanced immunogenic chemotherapy with reduced systemic toxicity. Our work provides an elegant strategy for persistently stimulating effective antitumor immunity to prevent postsurgical tumor recurrence and metastasis.