Breast Disease Center, The Affiliated Hospital of Qingdao University, No. 59, Haier Road, Qingdao, 266071, Shandong, People's Republic of China.
Department of Anesthesiology, The Affiliated Hospital of Qingdao University, No. 59, Haier Road, Qingdao, 266071, Shandong, People's Republic of China.
J Nanobiotechnology. 2022 Mar 2;20(1):96. doi: 10.1186/s12951-022-01255-6.
Despite extensive investigations on photothermal therapy, the clinical application is restricted due to poor stability, low therapeutic efficacy of photothermal therapy agents and its affinity loss in the multistep synthesis of delivery carriers. To address this, we designed an IR792-MCN@ZIF-8-PD-L1 siRNA (IM@ZP) nanoparticle drug delivery system. IM@ZP was prepared by in situ synthesis and physical adsorption, followed by characterization. Photothermal conversion ability of IM@ZP was assessed by irradiation of near-infrared (NIR) laser, followed by analysis of its effect on 4T1 cell viability, maturation of dendritic cells (DCs) and the secretion of related cytokines in vitro, and the changes of tumor infiltrating T cells and natural killer (NK) cells in vivo. Subcutaneous 4T1 tumor-bearing mouse and lung metastasis models were established to investigate the role of IM@ZP in killing tumor and inhibiting metastasis in vivo.
IM@ZP was uniform nanoparticles of 81.67 nm with the characteristic UV absorption peak of IR792, and could effectively adsorb PD-L1 siRNA. Under the irradiation of 808 nm laser, IM@ZP exhibited excellent photothermal performance. IM@ZP could be efficiently uptaken by 4T1 cells, and had high transfection efficiency of PD-L1 siRNA. Upon NIR laser irradiation, IM@ZP effectively killed 4T1 cells, upregulated HSP70 expression, induced DC maturation and increased secretion of TNF-α and IL-6 in vitro. Moreover, in vivo experimental results revealed that IM@ZP enhanced photothermal immunotherapy as shown by promoted tumor infiltrating CD8 + and CD4 + T cells and NK cells, and inhibited tumor growth and lung metastasis.
Together, biocompatible IM@ZP nanoparticles result in high photothermal immunotherapy efficiency and may have a great potential as a delivery system for sustained cancer therapy.
尽管对光热疗法进行了广泛的研究，但由于光热治疗剂的稳定性差、疗效低以及在递药载体的多步合成中亲和力丧失，其临床应用受到限制。为了解决这个问题，我们设计了一种 IR792-MCN@ZIF-8-PD-L1 siRNA（IM@ZP）纳米粒药物传递系统。IM@ZP 通过原位合成和物理吸附制备，然后进行表征。通过近红外（NIR）激光照射评估 IM@ZP 的光热转换能力，然后分析其对 4T1 细胞活力、树突状细胞（DC）成熟和相关细胞因子分泌的体外影响，以及肿瘤浸润性 T 细胞和自然杀伤（NK）细胞的体内变化。建立皮下 4T1 荷瘤小鼠和肺转移模型，研究 IM@ZP 在体内杀伤肿瘤和抑制转移的作用。
IM@ZP 是均一的 81.67nm 纳米粒，具有 IR792 的特征紫外吸收峰，并且可以有效地吸附 PD-L1 siRNA。在 808nm 激光照射下，IM@ZP 表现出优异的光热性能。IM@ZP 可以被 4T1 细胞有效摄取，并且具有 PD-L1 siRNA 的高转染效率。在 NIR 激光照射下，IM@ZP 有效地杀死 4T1 细胞，上调 HSP70 表达，诱导 DC 成熟并增加 TNF-α和 IL-6 的分泌。此外，体内实验结果表明，IM@ZP 通过促进肿瘤浸润性 CD8+和 CD4+T 细胞和 NK 细胞增强光热免疫治疗，抑制肿瘤生长和肺转移。
总之，生物相容性 IM@ZP 纳米粒具有高效的光热免疫治疗效果，可能作为一种持续癌症治疗的递送系统具有很大的潜力。
