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矿化卟啉金属有机框架用于改善肿瘤消除和联合免疫治疗。

Mineralized Porphyrin Metal-Organic Framework for Improved Tumor Elimination and Combined Immunotherapy.

机构信息

Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan 430072, P. R. China.

出版信息

ACS Nano. 2023 Jul 11;17(13):12471-12482. doi: 10.1021/acsnano.3c02126. Epub 2023 Jun 26.

Abstract

Calcium ion therapy is a potential anticancer treatment. However, the cellular calcium-buffering mechanism limited the effectiveness of calcium ion therapy. Here, we constructed a mineralized porphyrin metal-organic framework (PCa) to produce calcium ions and reactive oxygen species (ROS), which destroyed cell calcium buffering capacity and amplified the cell damage caused by calcium overload. In addition, PCa could induce cell immunogenic death to release tumor-associated antigen (TAA) and be used as an adjuvant. Thus, PCa could increase DC maturation and promote the antitumor activity of CD8 T cells. For mice experiment, PCa not only showed excellent tumor elimination on the subcutaneous breast tumor but also achieved obvious antimetastasis effect in the metastatic tumor model. This nanosystem could eliminate the primary tumor and boost effective antitumor immunotherapy for comprehensive anticancer treatment.

摘要

钙离子治疗是一种有潜力的抗癌治疗方法。然而,细胞内钙离子缓冲机制限制了钙离子治疗的效果。在这里,我们构建了一个矿化卟啉金属有机骨架(PCa)来产生钙离子和活性氧(ROS),破坏细胞钙缓冲能力,并放大钙超载引起的细胞损伤。此外,PCa 可以诱导细胞免疫原性死亡,释放肿瘤相关抗原(TAA),并作为佐剂使用。因此,PCa 可以增加树突状细胞的成熟,促进 CD8 T 细胞的抗肿瘤活性。在小鼠实验中,PCa 不仅在皮下乳腺癌模型中表现出优异的肿瘤消除效果,而且在转移性肿瘤模型中也取得了明显的抗转移效果。该纳米系统可以消除原发性肿瘤,并为全面抗癌治疗提供有效的抗肿瘤免疫治疗。

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