Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 300044, Taiwan.
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 300044, Taiwan; Department of Nanoengineering, University of California, San Diego, CA 92093, USA.
J Control Release. 2023 Aug;360:260-273. doi: 10.1016/j.jconrel.2023.06.033. Epub 2023 Jun 29.
T lymphocytes served as immune surveillance to suppress metastases by physically interacting with cancer cells. Whereas tumor immune privilege and heterogeneity protect immune attack, it limits immune cell infiltration into tumors, especially in invasive metastatic clusters. Here, a catalytic antigen-capture sponge (CAS) containing the catechol-functionalized copper-based metal organic framework (MOF) and chloroquine (CQ) for programming T cells infiltration is reported. The intravenously injected CAS accumulates at the tumor via the folic acid-mediated target and margination effect. In metastases, Fenton-like reaction induced by copper ions of CAS disrupts the intracellular redox potential, i.e., chemodynamic therapy (CDT), thereby reducing glutathione (GSH) levels. Furthermore, CQ helps inhibit autophagy by inducing lysosomal deacidification during CDT. This process leads to the breakdown of self-defense mechanisms, which exacerbates cytotoxicity. The therapies promote the liberation of tumor-associated antigens, such as neoantigens and damage-associated molecular patterns (DAMPs). Subsequently, the catechol groups present on CAS perform as antigen reservoirs and transport the autologous tumor-associated antigens to dendritic cells, resulting in prolonged immune activation. The CAS, which is capable of forming in-situ, serves as an antigen reservoir in CDT-mediated lung metastasis and leads to the accumulation of immune cells in metastatic clusters, thus hindering metastatic tumors.
T 淋巴细胞作为免疫监视，通过与癌细胞物理相互作用来抑制转移。然而，肿瘤免疫特权和异质性保护免疫攻击，限制了免疫细胞浸润到肿瘤中，特别是在侵袭性转移簇中。在这里，报道了一种包含儿茶酚功能化铜基金属有机骨架（MOF）和氯喹（CQ）的催化抗原捕获海绵（CAS），用于编程 T 细胞浸润。静脉注射的 CAS 通过叶酸介导的靶向和边缘效应积聚在肿瘤部位。在转移部位，CAS 中的铜离子诱导类 Fenton 反应破坏细胞内氧化还原电位，即化学动力学治疗（CDT），从而降低谷胱甘肽（GSH）水平。此外，CQ 通过在 CDT 期间诱导溶酶体去酸化有助于抑制自噬。这个过程导致自身防御机制的崩溃，从而加剧细胞毒性。这些治疗方法促进了肿瘤相关抗原的释放，如新生抗原和损伤相关分子模式（DAMPs）。随后，CAS 上存在的儿茶酚基团作为抗原储存库，并将自体肿瘤相关抗原运送到树突状细胞，从而导致免疫激活的延长。CAS 能够原位形成，在 CDT 介导的肺转移中作为抗原储存库，导致免疫细胞在转移簇中积聚，从而抑制转移瘤。
