Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, People's Republic of China.
Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
J Nanobiotechnology. 2021 Dec 11;19(1):415. doi: 10.1186/s12951-021-01158-y.
Immunochemotherapy is a potent anti-tumor strategy, however, how to select therapeutic drugs to enhance the combined therapeutic effect still needs to be explored. METHODS AND RESULTS: Herein, a magnetic resonance nanoprobe (MnP@Lip) with STING (Stimulator of INterferon Genes) activation character was synthesized and co-administered with platinum-based chemotherapeutics for enhanced immunochemotherapy. MnP@Lip nanoparticles was prepared by simple fabrication process with good reproducibility, pH-sensitive drug release behavior and biocompatibility. In vitro experiments elucidated that Mn can promote the polarization of M0 and/or M2 macrophages to M1 phenotype, and promote the maturation of BMDC cells. Upon Mn treatment, the STING pathway was activated in tumor cells, mouse lung epithelial cells, and immune cells. More importantly, anti-tumor experiments in vivo proved that MnP@Lip combined with platinum-based chemotherapeutics increased T cells infiltration in the tumor microenvironment, and inhibited tumor growth in the orthotopic therapeutic and postoperative tumor models.
This kind of therapeutic strategy that combined MnP@Lip nanoparticles with platinum-based chemotherapeutics may provide a novel insight for immunochemotherapy.
免疫化学疗法是一种有效的抗肿瘤策略，然而，如何选择治疗药物以增强联合治疗效果仍需探索。
在此，我们合成了一种具有 STING（干扰素基因刺激物）激活特性的磁共振纳米探针（MnP@Lip），并与铂类化疗药物联合使用以增强免疫化学疗法。MnP@Lip 纳米颗粒通过简单的制造工艺制备，具有良好的重现性、pH 敏感性药物释放行为和生物相容性。体外实验表明，Mn 可以促进 M0 和/或 M2 巨噬细胞向 M1 表型极化，并促进 BMDC 细胞的成熟。在 Mn 处理后，STING 途径在肿瘤细胞、小鼠肺上皮细胞和免疫细胞中被激活。更重要的是，体内抗肿瘤实验证明，MnP@Lip 联合铂类化疗药物增加了肿瘤微环境中的 T 细胞浸润，并抑制了原位治疗和术后肿瘤模型中的肿瘤生长。
这种将 MnP@Lip 纳米颗粒与铂类化疗药物联合使用的治疗策略可能为免疫化学疗法提供新的思路。
