School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore, 637371, Singapore.
Adv Mater. 2024 Nov;36(45):e2408242. doi: 10.1002/adma.202408242. Epub 2024 Sep 3.
Sonodynamic therapy can trigger immunogenic cell death to augment immunotherapy, benefiting from its superior spatiotemporal selectivity and non-invasiveness. However, the practical applications of sonosensitizers are hindered by their low efficacy in killing cancer cells and activating immune responses. Here, two US Food and Drug Administration-approved drug ligands (ferricyanide and nitroprusside) and two types of metals (copper/iron) are selected to construct a bimetal-biligand framework (Cu[PBA-NO]). Through elaborate regulation of multiple metal/ligand coordination, the systemically administered Cu[PBA-NO] nanoagent shows sono-catalytic and NO release ability under ultrasound irradiation, which can be used for effective sono-immunotherapy. Moreover, Cu[PBA-NO] can downregulate intracellular glutathione levels that would destroy intracellular redox homeostasis and facilitate reactive oxygen species accumulation. The released tumor-associated antigens subsequently facilitate dendritic cell maturation within the tumor-draining lymph node, effectively initiating a T cell-mediated immune response and thereby bolstering the capacity to identify and combat cancer cells. This study paves a new avenue for the efficient cancer sono-immunotherapy.
声动力学疗法可以触发免疫原性细胞死亡以增强免疫疗法，受益于其优越的时空选择性和非侵入性。然而，声敏剂的实际应用受到其在杀死癌细胞和激活免疫反应方面的低效率的阻碍。在这里，选择了两种美国食品和药物管理局批准的药物配体（铁氰化物和硝普盐）和两种类型的金属（铜/铁）来构建双金属双配体框架（Cu[PBA-NO]）。通过对多种金属/配体配位的精心调节，系统给予的 Cu[PBA-NO]纳米剂在超声辐射下显示出声催化和 NO 释放能力，可用于有效的声免疫治疗。此外，Cu[PBA-NO]可以下调细胞内谷胱甘肽水平，破坏细胞内氧化还原平衡并促进活性氧物质的积累。随后释放的肿瘤相关抗原促进肿瘤引流淋巴结内树突状细胞的成熟，有效引发 T 细胞介导的免疫反应，从而增强识别和抗击癌细胞的能力。这项研究为有效的癌症声免疫治疗开辟了新途径。
