The Second Affiliated Hospital of Chongqing Medical University & Chongqing Key Laboratory of Ultrasound Molecular Imaging, Chongqing, 400010, China.
Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
Biomaterials. 2019 Oct;219:119370. doi: 10.1016/j.biomaterials.2019.119370. Epub 2019 Jul 18.
While theranostic nanoparticle (TNP)-based photothermal therapy (PTT) exhibits prominent promise for cancer therapy, metastatic cancers remain one of the main obstacles of effective PTT. Immunotherapy has been developed vigorously to inhibit metastatic cancers, but the heterogeneity of patients and the complexities of manufacturing cancer vaccines significantly hinder its further clinical applications. Herein, a photothermally triggered immunotherapeutic paradigm under imaging guidance was designed based on magnetic-responsive immunostimulatory nanoagents (MINPs) loaded with superparamagnetic iron oxide (SPIO) nanoparticles and cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODNs). The fabricated MINPs with the clinically approved components acted not only as a contrast agent for photoacoustic (PA)/magnetic resonance (MR) bimodal imaging but also as a magnetic-targeting therapeutic agent for photothermally triggered immunotherapy. Under external magnetic fields, the MINPs showed a great magnetic-targeting ability, leading to high accumulation of the photoabsorber (SPIO) and the immunoadjuvant (CpG ODNs) in the tumors for precise bimodal imaging guidance. More importantly, the excellent photothermal conversion effect of the MINPs upon near-infrared (NIR) exposure enabled the effective photothermal destruction of the primary tumors, releasing tumor-associated antigens and showing 'autologous cancer vaccine'-like functions, thus activating robust antitumor immune responses, especially in the presence of CpG ODN-containing immunostimulatory nanoagents. Such generated immune responses can further attack the remaining tumors and distant metastatic tumors in mice. This work provides an imaging-guided photothermally triggered immunotherapeutic strategy based on multifunctional MINPs to effectively eliminate primary tumors and inhibit metastatic tumors simultaneously with high specificity, easy maneuverability and favorable biocompatibility. This strategy may potentially be applicable for precise individualized diagnosis and therapy of various tumors.
虽然基于治疗诊断一体化纳米粒子（TNP）的光热疗法（PTT）在癌症治疗方面表现出了显著的前景，但转移性癌症仍然是有效 PTT 的主要障碍之一。免疫疗法已被大力开发以抑制转移性癌症，但患者的异质性和癌症疫苗的复杂性严重阻碍了其进一步的临床应用。在此，设计了一种基于载超顺磁性氧化铁（SPIO）纳米颗粒和胞嘧啶-磷酸-鸟嘌呤寡脱氧核苷酸（CpG ODN）的磁响应免疫刺激纳米制剂（MINPs）的光热触发免疫治疗模式，该模式在影像引导下进行。所制备的具有临床批准成分的 MINPs 不仅可以作为光声（PA）/磁共振（MR）双模态成像的造影剂，还可以作为光热触发免疫治疗的磁靶向治疗剂。在外部磁场下，MINPs 表现出很强的磁靶向能力，导致光吸收剂（SPIO）和免疫佐剂（CpG ODN）在肿瘤中的高积累，从而实现精确的双模态成像引导。更重要的是，MINPs 在近红外（NIR）照射下的优异光热转换效果使原发肿瘤能够有效光热破坏，释放肿瘤相关抗原，并表现出“自体癌症疫苗”样功能，从而激活强大的抗肿瘤免疫反应，特别是在含有 CpG ODN 的免疫刺激纳米制剂存在的情况下。这种免疫反应可以进一步攻击小鼠体内剩余的肿瘤和远处转移的肿瘤。这项工作提供了一种基于多功能 MINPs 的影像引导光热触发免疫治疗策略，可以在高特异性、易操作性和良好的生物相容性的情况下，有效地消除原发肿瘤并抑制转移肿瘤。该策略可能有望应用于各种肿瘤的精确个体化诊断和治疗。
